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1
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Monaghan NP, Duckett KA, Nguyen SA, Newman JG, Albergotti WG, Kejner AE. Vascular events in patients with head and neck cancer: A systematic review and meta-analysis. Head Neck 2024; 46:1557-1572. [PMID: 38334324 DOI: 10.1002/hed.27675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 01/02/2024] [Accepted: 01/29/2024] [Indexed: 02/10/2024] Open
Abstract
OBJECTIVE To assess the incidence of vascular events in patients with head and neck cancer. REVIEW METHODS Primary studies identified through April 2023. Meta-analysis was performed. RESULTS There were 146 studies included in the systematic review. Rates of events were collected in the overall group, those with chemoprophylaxis, and those that underwent surgery, radiation, or chemotherapy. Of 1 184 160 patients, 4.3% had a vascular event. Radiation therapy had highest risk of overall events and stroke when compared to surgery and chemotherapy. Chemotherapy had a higher risk of stroke and overall events when compared to surgery. CONCLUSIONS Vascular events occur in 4%-5% of patients with head and neck cancer. Our data does not support the use of routine anticoagulation. Patients undergoing radiation therapy had the highest frequency of events.
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Affiliation(s)
- Neil P Monaghan
- Department of Otolaryngology, Medical University of South Carolina, Charleston, South Carolina, USA
- College of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Kelsey A Duckett
- Department of Otolaryngology, Medical University of South Carolina, Charleston, South Carolina, USA
- College of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Shaun A Nguyen
- Department of Otolaryngology, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Jason G Newman
- Department of Otolaryngology, Medical University of South Carolina, Charleston, South Carolina, USA
| | - W Greer Albergotti
- Department of Otolaryngology, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Alexandra E Kejner
- Department of Otolaryngology, Medical University of South Carolina, Charleston, South Carolina, USA
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2
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Meijer AJ, Diepstraten FA, Ansari M, Bouffet E, Bleyer A, Fresneau B, Geller JI, Huitema AD, Kogner P, Maibach R, O'Neill AF, Papadakis V, Rajput KM, Veal GJ, Sullivan M, van den Heuvel-Eibrink MM, Brock PR. Use of Sodium Thiosulfate as an Otoprotectant in Patients With Cancer Treated With Platinum Compounds: A Review of the Literature. J Clin Oncol 2024; 42:2219-2232. [PMID: 38648563 PMCID: PMC11191063 DOI: 10.1200/jco.23.02353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 01/05/2024] [Accepted: 02/07/2024] [Indexed: 04/25/2024] Open
Abstract
PURPOSE Hearing loss occurs in 50%-70% of children treated with cisplatin. Scientific efforts have led to the recent approval of a pediatric formula of intravenous sodium thiosulfate (STS) for otoprotection by the US Food and Drug Administration, the European Medicines Agency, and the Medicines and Health Regulatory Authority in the United Kingdom. To inform stakeholders regarding the clinical utility of STS, the current review summarizes available literature on the efficacy, pharmacokinetics (PK), and safety of systemic STS to minimize cisplatin-induced hearing loss (CIHL). DESIGN A comprehensive narrative review is presented. RESULTS Thirty-one articles were summarized. Overall, systemic STS effectively reduces CIHL in the preclinical and controlled clinical study settings, in both adults and children with cancer. The extent of CIHL reduction depends on the timing and dosing of STS in relation to cisplatin. Both preclinical and clinical data suggest that systemic STS may affect plasma platinum levels, but studies are inconclusive. Delayed systemic administration of STS, at 6 hours after the cisplatin infusion, does not affect cisplatin-induced inhibition of tumor growth or cellular cytotoxicity in the preclinical setting, nor affect cisplatin efficacy and survival in children with localized disease in the clinical setting. CONCLUSION Systemic administration of STS effectively reduces the development and degree of CIHL in both the preclinical and clinical settings. More studies are needed on the PK of STS and cisplatin drug combinations, the efficacy and safety of STS in patients with disseminated disease, and the ability of STS to prevent further deterioration of pre-established hearing loss.
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Affiliation(s)
| | | | - Marc Ansari
- Cansearch Research Platform for Pediatric Oncology and Hematology, Faculty of Medicine, Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, Division of Pediatric Oncology and Hematology, Department of Women, Child and Adolescent, University Geneva Hospitals, Geneva, Switzerland
| | - Eric Bouffet
- Division of Pediatric Neuro-Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Archie Bleyer
- Department of Radiation Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, Canada
| | - Brice Fresneau
- Department of Children and Adolescents Oncology, Gustave Roussy, University Paris Saclay and Radiation Epidemiology Team, CESO, Inserm U1018, Villejuif, France
| | - James I. Geller
- Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Alwin D.R. Huitema
- Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
- Department of Pharmacy and Pharmacology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands
- Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Per Kogner
- Department of Pediatric Oncology and Childhood Cancer Research Unit, Karolinska Institutet, Stockholm, Sweden
| | | | - Allison F. O'Neill
- Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA
| | - Vassilios Papadakis
- Department of Pediatric Hematology-Oncology (TAO), Agia Sofia Children's Hospital, Athens, Greece
| | - Kaukab M. Rajput
- Department of Pediatric Audiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
| | - Gareth J. Veal
- Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Michael Sullivan
- Children's Cancer Centre and Department of Pediatric Oncology, Royal Children's Hospital, Melbourne, Victoria, Australia
| | - Marry M. van den Heuvel-Eibrink
- Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
- Wilhelmina Childrens' Hospital, Division of Child Health, Utrecht, the Netherlands
| | - Penelope R. Brock
- Department of Pediatric Oncology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
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3
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Ono T, Tanaka N, Chitose SI, Tanoue S, Kurita T, Sueyoshi S, Fukahori M, Miyata Y, Muraki K, Tsuji C, Ogo E, Hattori C, Sato K, Abe T, Umeno H. Comparative Treatment Outcome in T3N0 Glottic Cancer With and Without Vocal Fold Fixation Receiving Radiation Therapy and Concurrent Low-Dose Intra-Arterial Cisplatin Infusion. Ann Otol Rhinol Laryngol 2021; 131:897-904. [PMID: 34565187 DOI: 10.1177/00034894211047789] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVES Selective radiotherapy and concomitant intra-arterial cisplatin infusion (m-RADPLAT) with a lower cisplatin dosage have been performed for organ and function preservation in patients with locally advanced squamous cell carcinoma of the larynx (SCC-L), and results showing a lower rate of adverse events have been reported. This study evaluated the treatment outcomes of patients with T3N0 glottic SCC-L with or without vocal fold fixation (VFF) who were treated with m-RADPLAT. METHODS We retrospectively reviewed the data of 33 patients with T3N0 SCC-L who received m-RADPLAT. RESULTS The vocal fold in patients with VFF 3 months after completing m-RADPLAT resumed normal movement in 15 patients (83%) and persisted fixation in 3 (17%). The 3-year local control, laryngeal cancer-specific survival, and overall survival rates of patients with or without VFF were 88.9% and 86.7%, 94.1% and 93.3%, and 88.9% and 86.7%, respectively. Additionally, the 3-year freedom from laryngectomy, laryngectomy-free survival, and laryngo-esophageal dysfunction-free survival rates of patients with or without VFF were 94.4% and 86.7%, 88.9% and 73.3%, and 83.3% and 73.3%, respectively. Grade 3 or higher toxicities were observed in all patients: leukopenia in 4 patients (12%), neutropenia in 5 (15%), anemia in 2 (6%), thrombocytopenia in 3 (9%), and mucositis in 2 (6%). CONCLUSIONS This study demonstrated that m-RADPLAT yielded VFF improvement and a favorable survival while maintaining laryngeal function not only in patients with T3N0 glottic SCC-L without VFF but also in patients with VFF.
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Affiliation(s)
- Takeharu Ono
- Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Kurume University, Kurume, Japan
| | - Norimitsu Tanaka
- Department of Radiology, School of Medicine, Kurume University, Kurume, Japan
| | - Shun-Ichi Chitose
- Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Kurume University, Kurume, Japan
| | - Syuichi Tanoue
- Department of Radiology, School of Medicine, Kurume University, Kurume, Japan
| | - Takashi Kurita
- Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Kurume University, Kurume, Japan
| | - Shintarou Sueyoshi
- Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Kurume University, Kurume, Japan
| | - Mioko Fukahori
- Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Kurume University, Kurume, Japan
| | - Yusaku Miyata
- Department of Radiology, School of Medicine, Kurume University, Kurume, Japan
| | - Koichiro Muraki
- Department of Radiology, School of Medicine, Kurume University, Kurume, Japan
| | - Chiyoko Tsuji
- Department of Radiology, School of Medicine, Kurume University, Kurume, Japan
| | - Etsuyo Ogo
- Department of Radiology, School of Medicine, Kurume University, Kurume, Japan
| | - Chikayuki Hattori
- Department of Radiology, School of Medicine, Kurume University, Kurume, Japan
| | - Kiminobu Sato
- Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Kurume University, Kurume, Japan
| | - Toshi Abe
- Department of Radiology, School of Medicine, Kurume University, Kurume, Japan
| | - Hirohito Umeno
- Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Kurume University, Kurume, Japan
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4
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Dysphagia, trismus and speech impairment following radiation-based treatment for advanced stage oropharyngeal carcinoma: a one-year prospective evaluation. Eur Arch Otorhinolaryngol 2021; 279:1003-1027. [PMID: 34043065 DOI: 10.1007/s00405-021-06870-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 05/04/2021] [Indexed: 12/22/2022]
Abstract
OBJECTIVE The objective was to assess swallowing, mouth opening and speech function during the first year after radiation-based treatment (RT(+)) after introduction of a dedicated preventive rehabilitation program for stage III-IV oropharyngeal carcinoma (OPC). METHODS Swallowing, mouth opening and speech function were collected before and at six- and twelve-month follow-up after RT(+) for OPC as part of ongoing prospective assessments by speech-language pathologists . RESULTS Objective and patient-perceived function deteriorated until 6 months and improved until 12 months after treatment, but did not return to baseline levels with 25%, 20% and 58% of the patients with objective dysphagia, trismus and speech problems, respectively. Feeding tube dependency and pneumonia prevalence was low. CONCLUSION Despite successful implementation, a substantial proportion of patients still experience functional limitations after RT(+) for OPC, suggesting room for improvement of the current rehabilitation program. Pretreatment sarcopenia seems associated with worse functional outcomes and might be a relevant new target for rehabilitation strategies.
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5
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Casanova AG, Hernández-Sánchez MT, Martínez-Salgado C, Morales AI, Vicente-Vicente L, López-Hernández FJ. A meta-analysis of preclinical studies using antioxidants for the prevention of cisplatin nephrotoxicity: implications for clinical application. Crit Rev Toxicol 2020; 50:780-800. [PMID: 33170047 DOI: 10.1080/10408444.2020.1837070] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Cisplatin is an effective chemotherapeutic drug whose clinical use and efficacy are limited by its nephrotoxicity, which affects mainly the renal tubules and vasculature. It accumulates in proximal and distal epithelial tubule cells and causes oxidative stress-mediated cell death and malfunction. Consequently, many antioxidants have been tested for their capacity to prevent cisplatin nephrotoxicity. In this study, we made a systematic review of the literature and meta-analyzed 152 articles, which tested the nephroprotective effect of isolated compounds or mixtures of natural origin on cisplatin nephrotoxicity in preclinical models. This meta-analysis identified the most effective candidates and examined the efficacy obtained by antioxidants administered by the oral and intraperitoneal routes. By comparing with a recent, similar meta-analysis performed on clinical studies, this article identifies a disconnection between preclinical and clinical research, and contextualizes, discusses, and integrates the existing preclinical information toward the optimized selection of candidates to be further explored (clinical level). Despite proved efficacy, this article discusses the barriers limiting the clinical development of natural mixtures, such as those in extracts from Calendula officinalis flowers and Heliotropium eichwaldii roots. On the contrary, isolated compounds are more straightforward candidates, among which arjunolic acid and quercetin stand out in this meta-analysis.
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Affiliation(s)
- Alfredo G Casanova
- Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.,Department of Physiology and Pharmacology, University of Salamanca (USAL), Salamanca, Spain.,Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León (IECSCYL), Soria, Spain.,Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain.,National Network for Kidney Research REDINREN, Instituto de Salud Carlos III, Madrid, Spain
| | - M Teresa Hernández-Sánchez
- Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.,Department of Physiology and Pharmacology, University of Salamanca (USAL), Salamanca, Spain.,Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León (IECSCYL), Soria, Spain.,Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain.,National Network for Kidney Research REDINREN, Instituto de Salud Carlos III, Madrid, Spain
| | - Carlos Martínez-Salgado
- Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.,Department of Physiology and Pharmacology, University of Salamanca (USAL), Salamanca, Spain.,Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León (IECSCYL), Soria, Spain.,Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain.,National Network for Kidney Research REDINREN, Instituto de Salud Carlos III, Madrid, Spain
| | - Ana I Morales
- Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.,Department of Physiology and Pharmacology, University of Salamanca (USAL), Salamanca, Spain.,Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain.,National Network for Kidney Research REDINREN, Instituto de Salud Carlos III, Madrid, Spain.,Group of Biomedical Research on Critical Care (BioCritic), Valladolid, Spain
| | - Laura Vicente-Vicente
- Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.,Department of Physiology and Pharmacology, University of Salamanca (USAL), Salamanca, Spain.,Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain.,National Network for Kidney Research REDINREN, Instituto de Salud Carlos III, Madrid, Spain
| | - Francisco J López-Hernández
- Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.,Department of Physiology and Pharmacology, University of Salamanca (USAL), Salamanca, Spain.,Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León (IECSCYL), Soria, Spain.,Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain.,National Network for Kidney Research REDINREN, Instituto de Salud Carlos III, Madrid, Spain.,Group of Biomedical Research on Critical Care (BioCritic), Valladolid, Spain
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6
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Essers PB, van der Heijden M, Vossen D, de Roest RH, Leemans CR, Brakenhoff RH, van den Brekel MW, Bartelink H, Verheij M, Vens C. Ovarian cancer-derived copy number alterations signatures are prognostic in chemoradiotherapy-treated head and neck squamous cell carcinoma. Int J Cancer 2020; 147:1732-1739. [PMID: 32167160 PMCID: PMC7496441 DOI: 10.1002/ijc.32962] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 01/17/2020] [Accepted: 02/11/2020] [Indexed: 12/19/2022]
Abstract
DNA copy number alterations (CNAs) are frequent in cancer, and recently developed CNA signatures revealed their value in molecular tumor stratification for patient prognosis and platinum resistance prediction in ovarian cancer. Head and neck squamous cell carcinoma (HNSCC) is also characterized by high CNAs. In this study, we determined CNA in 173 human papilloma virus-negative HNSCC from a Dutch multicenter cohort by low-coverage whole genome sequencing and tested the prognostic value of seven cancer-derived CNA signatures for these cisplatin- and radiotherapy-treated patients. We find that a high CNA signature 1 (s1) score is associated with low values for all other signatures and better patient outcomes in the Dutch cohorts and The Cancer Genome Atlas HNSCC data set. High s5 and s7 scores are associated with increased distant metastasis rates and high s6 scores with poor overall survival. High cumulative cisplatin doses result in improved outcomes in chemoradiotherapy-treated HNSCC patients. Here we find that tumors high in s1 or low in s6 are most responsive to a change in cisplatin dose. High s5 values, however, significantly increase the risk for metastasis in patients with low cumulative cisplatin doses. Together this suggests that the processes causing these CNA signatures affect cisplatin response in HNSCC. In conclusion, CNA signatures derived from a different cancer type were prognostic and associated with cisplatin response in HNSCC, suggesting they represent underlying molecular processes that define patient outcome.
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Affiliation(s)
- Paul B.M. Essers
- Division of Cell BiologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
| | - Martijn van der Heijden
- Division of Cell BiologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
- Department of Head and Neck Oncology and SurgeryThe Netherlands Cancer InstituteAmsterdamThe Netherlands
| | - David Vossen
- Division of Cell BiologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
| | - Reinout H. de Roest
- Amsterdam UMCVrije Universiteit Amsterdam, Otolaryngology/Head and Neck Surgery, Cancer Center AmsterdamThe Netherlands
| | - C. René Leemans
- Amsterdam UMCVrije Universiteit Amsterdam, Otolaryngology/Head and Neck Surgery, Cancer Center AmsterdamThe Netherlands
| | - Ruud H. Brakenhoff
- Amsterdam UMCVrije Universiteit Amsterdam, Otolaryngology/Head and Neck Surgery, Cancer Center AmsterdamThe Netherlands
| | | | - Harry Bartelink
- Department of Radiation OncologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
| | - Marcel Verheij
- Division of Cell BiologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
- Department of Radiation OncologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
| | - Conchita Vens
- Division of Cell BiologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
- Department of Radiation OncologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
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7
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Kamran M, Wallace AN, Adewumi A. Interventional Management of Head and Neck Tumors. Semin Intervent Radiol 2020; 37:157-165. [PMID: 32419728 DOI: 10.1055/s-0040-1709157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Advancements in medical imaging and device technology allow minimal invasive procedures for the diagnosis and treatment of various disorders. For the management of tumors in head and neck region, these image-guided interventions play essential role in the often used multidisciplinary approach. Tissue sampling under ultrasound or computed tomography guidance is generally the first step to reach a pathological diagnosis. For head and neck tumors with high vascularity, embolization using particulate matter, liquid embolic agents, or coils is used to achieve successful tumor resection with minimal blood loss. Hemorrhage related to head and neck tumors can be evaluated and managed with endovascular techniques with minimal morbidity and mortality. Intra-arterial chemotherapy, radiofrequency ablation, and cryotherapy are new techniques for the management of advanced head and neck cancer which may serve as an alternative to achieve locoregional control and survival when curative resection may not be feasible.
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Affiliation(s)
- Mudassar Kamran
- Department of Radiology, UAMS College of Medicine, Little Rock, Arkansas
| | - Adam N Wallace
- Department of Neurointerventional Surgery, Ascension Columbia St. Mary's Hospital, Milwaukee, Wisconsin
| | - Amole Adewumi
- Department of Radiology, UAMS College of Medicine, Little Rock, Arkansas
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8
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Hasegawa H, Kaneko T, Kanno C, Endo M, Yamazaki M, Kitabatake T, Monma T, Takeishi E, Sato E, Kano M. Preoperative intra-arterial chemotherapy with docetaxel, cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil for oral squamous cell carcinoma. Int J Oral Maxillofac Surg 2020; 49:984-992. [PMID: 32070653 DOI: 10.1016/j.ijom.2020.01.024] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Revised: 11/30/2019] [Accepted: 01/20/2020] [Indexed: 11/29/2022]
Abstract
The objectives of this study were to evaluate survival in 141 patients with stage II-IV oral squamous cell carcinoma (OSCC) treated with preoperative intra-arterial chemotherapy with docetaxel, cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil (IADCPIVF) via the superficial temporal artery, and to clarify the prognostic factors. The study population included 59 patients with stage II OSCC, 34 with stage III, and 48 with stage IV. After IADCPIVF, 139 patients underwent surgery; minimally invasive surgeries (MIS) including excisional biopsy were performed on 96 patients with a remarkably good response to IADCPIVF. The primary tumour response rate was 99.3% (complete response rate 56.7%, good partial response rate 17.0%, fair partial response rate 25.5%). Additionally, there were no serious adverse events associated with IADCPIVF. The 5-year overall survival rate was 74.6% (stage II 83.6%, stage III 72.7%, stage IV 64.8%). In the multivariate analysis of survival, T classification and clinical tumour response were significant prognostic factors. Eight (8.3%) of the patients who received MIS had primary recurrence and six were salvaged. In conclusion, IADCPIVF is safe and efficacious for treating OSCC, and MIS could reduce the extent of primary tumour resection in the case of a remarkably good response.
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Affiliation(s)
- H Hasegawa
- Department of Dentistry and Oral Surgery, Fukushima Medical University, School of Medicine, Fukushima, Japan.
| | - T Kaneko
- Department of Dentistry and Oral Surgery, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - C Kanno
- Department of Dentistry and Oral Surgery, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - M Endo
- Department of Dentistry and Oral Surgery, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - M Yamazaki
- Department of Dentistry and Oral Surgery, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - T Kitabatake
- Department of Dentistry and Oral Surgery, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - T Monma
- Department of Dentistry and Oral Surgery, Fukushima Medical University, School of Medicine, Fukushima, Japan
| | - E Takeishi
- Department of Dentistry and Oral Surgery, Tsuruoka Municipal Shonai Hospital, Tsuruoka, Japan
| | - E Sato
- Department of Dentistry, Kashima Hospital, Ibaraki, Japan
| | - M Kano
- Department of Head and Neck, Facial Surgery, Ohara General Hospital, Fukushima, Japan
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9
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Yang X, Ren H, Yu W, Zhang X, Sun Y, Shao Y, Zhang L, Li H, Yang X, Fu J. Analysis of Clinical Target Volume Delineation in Local-regional Failure of Nasopharyngeal Carcinoma after Intensity-modulated Radiotherapy. J Cancer 2020; 11:1968-1975. [PMID: 32194808 PMCID: PMC7052868 DOI: 10.7150/jca.39588] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2019] [Accepted: 12/26/2019] [Indexed: 12/05/2022] Open
Abstract
OBJECTIVE: To analyze the pattern of local failure in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT) and find a more reasonable delineation of the clinical target volume (CTV). METHODS AND MATERIALS: A total of 212 patients with non-metastatic NPC who underwent IMRT were analyzed. Radiation therapy was run at a total dose of 66-74 Gy (2.0-2.2 Gy fractions). The follow-up of local recurrence and the recurrence-related features were analyzed for the original treatment situation. The failures were delimited as “in-field failure” if Vrecur within the 95% isodose curve (V95%) was ≥95%; “marginal failure” if V95% was less than 95% and not less than 20%; or “out-field failure” if V95% was< 20%. Kaplan-Meier method was used to calculate the survival rates. RESULTS: The median follow-up was 43.4 months. The 5-year local relapse-free survival and overall survival rates were 85.6 and 77.8%, respectively. A total of 18 patients have relapsed. The in-field failure, marginal failure, and out-field failure accounted for 83.3%, 11.1%, and 5.6%, respectively. The site of recurrence was basically in the high dose area. CONCLUSION: These findings suggested that IMRT provide a good local control for patients with NPC, and the in-field failure is the main mode. A wide range of CTV cannot prevent the local recurrence, narrowing the CTV to protect the adjacent organs should be taken into consideration.
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Affiliation(s)
- Xiaojing Yang
- Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai, 200233, China
| | - Hanru Ren
- Department of Orthopedics, Shanghai Pudong Hospital, Fudan University, Pudong Medical Center, Shanghai 201300, P.R China
| | - Weiwei Yu
- Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai, 200233, China
| | - Xiulong Zhang
- Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai, 200233, China
| | - Yi Sun
- Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai, 200233, China
| | - Yuhui Shao
- Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai, 200233, China
| | - Lihua Zhang
- Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai, 200233, China
| | - Hongling Li
- Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai, 200233, China
| | - Xinmiao Yang
- Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai, 200233, China
| | - Jie Fu
- Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai, 200233, China
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10
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van der Heijden M, Essers PBM, de Jong MC, de Roest RH, Sanduleanu S, Verhagen CVM, Hamming-Vrieze O, Hoebers F, Lambin P, Bartelink H, Leemans CR, Verheij M, Brakenhoff RH, van den Brekel MWM, Vens C. Biological Determinants of Chemo-Radiotherapy Response in HPV-Negative Head and Neck Cancer: A Multicentric External Validation. Front Oncol 2020; 9:1470. [PMID: 31998639 PMCID: PMC6966332 DOI: 10.3389/fonc.2019.01470] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 12/09/2019] [Indexed: 12/20/2022] Open
Abstract
Purpose: Tumor markers that are related to hypoxia, proliferation, DNA damage repair and stem cell-ness, have a prognostic value in advanced stage HNSCC patients when assessed individually. Here we aimed to evaluate and validate this in a multifactorial context and assess interrelation and the combined role of these biological factors in determining chemo-radiotherapy response in HPV-negative advanced HNSCC. Methods: RNA sequencing data of pre-treatment biopsy material from 197 HPV-negative advanced stage HNSCC patients treated with definitive chemoradiotherapy was analyzed. Biological parameter scores were assigned to patient samples using previously generated and described gene expression signatures. Locoregional control rates were used to assess the role of these biological parameters in radiation response and compared to distant metastasis data. Biological factors were ranked according to their clinical impact using bootstrapping methods and multivariate Cox regression analyses that included clinical variables. Multivariate Cox regression analyses comprising all biological variables were used to define their relative role among all factors when combined. Results: Only few biomarker scores correlate with each other, underscoring their independence. The different biological factors do not correlate or cluster, except for the two stem cell markers CD44 and SLC3A2 (r = 0.4, p < 0.001) and acute hypoxia prediction scores which correlated with T-cell infiltration score, CD8+ T cell abundance and proliferation scores (r = 0.52, 0.56, and 0.6, respectively with p < 0.001). Locoregional control association analyses revealed that chronic (Hazard Ratio (HR) = 3.9) and acute hypoxia (HR = 1.9), followed by stem cell-ness (CD44/SLC3A2; HR = 2.2/2.3), were the strongest and most robust determinants of radiation response. Furthermore, multivariable analysis, considering other biological and clinical factors, reveal a significant role for EGFR expression (HR = 2.9, p < 0.05) and T-cell infiltration (CD8+T-cells: HR = 2.2, p < 0.05; CD8+T-cells/Treg: HR = 2.6, p < 0.01) signatures in locoregional control of chemoradiotherapy-treated HNSCC. Conclusion: Tumor acute and chronic hypoxia, stem cell-ness, and CD8+ T-cell parameters are relevant and largely independent biological factors that together contribute to locoregional control. The combined analyses illustrate the additive value of multifactorial analyses and support a role for EGFR expression analysis and immune cell markers in addition to previously validated biomarkers. This external validation underscores the relevance of biological factors in determining chemoradiotherapy outcome in HNSCC.
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Affiliation(s)
- Martijn van der Heijden
- Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, Netherlands.,Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Amsterdam, Netherlands
| | - Paul B M Essers
- Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, Netherlands.,Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands
| | - Monique C de Jong
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands
| | - Reinout H de Roest
- Amsterdam UMC, Vrije Universiteit Amsterdam, Otolaryngology/Head and Neck Surgery, Cancer Center Amsterdam, Amsterdam, Netherlands
| | - Sebastian Sanduleanu
- Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, Netherlands
| | - Caroline V M Verhagen
- Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, Netherlands.,Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Amsterdam, Netherlands
| | - Olga Hamming-Vrieze
- Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Amsterdam, Netherlands
| | - Frank Hoebers
- Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, Netherlands
| | - Philippe Lambin
- The D-Lab and The M-Lab, Department of Precision Medicine, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, Netherlands
| | - Harry Bartelink
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands
| | - C René Leemans
- Amsterdam UMC, Vrije Universiteit Amsterdam, Otolaryngology/Head and Neck Surgery, Cancer Center Amsterdam, Amsterdam, Netherlands
| | - Marcel Verheij
- Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, Netherlands.,Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands.,Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Ruud H Brakenhoff
- Amsterdam UMC, Vrije Universiteit Amsterdam, Otolaryngology/Head and Neck Surgery, Cancer Center Amsterdam, Amsterdam, Netherlands
| | - Michiel W M van den Brekel
- Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Amsterdam, Netherlands.,Department of Oral and Maxillofacial Surgery, Amsterdam UMC, Academic Medical Center, Amsterdam, Netherlands
| | - Conchita Vens
- Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, Netherlands.,Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands
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11
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Essers PBM, van der Heijden M, Verhagen CVM, Ploeg EM, de Roest RH, Leemans CR, Brakenhoff RH, van den Brekel MWM, Bartelink H, Verheij M, Vens C. Drug Sensitivity Prediction Models Reveal a Link between DNA Repair Defects and Poor Prognosis in HNSCC. Cancer Res 2019; 79:5597-5611. [PMID: 31515237 DOI: 10.1158/0008-5472.can-18-3388] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Revised: 05/16/2019] [Accepted: 09/05/2019] [Indexed: 11/16/2022]
Abstract
Head and neck squamous cell carcinoma (HNSCC) is characterized by the frequent manifestation of DNA crosslink repair defects. We established novel expression-based DNA repair defect markers to determine the clinical impact of such repair defects. Using hypersensitivity to the DNA crosslinking agents, mitomycin C and olaparib, as proxies for functional DNA repair defects in a panel of 25 HNSCC cell lines, we applied machine learning to define gene expression models that predict repair defects. The expression profiles established predicted hypersensitivity to DNA-damaging agents and were associated with mutations in crosslink repair genes, as well as downregulation of DNA damage response and repair genes, in two independent datasets. The prognostic value of the repair defect prediction profiles was assessed in two retrospective cohorts with a total of 180 patients with advanced HPV-negative HNSCC, who were treated with cisplatin-based chemoradiotherapy. DNA repair defects, as predicted by the profiles, were associated with poor outcome in both patient cohorts. The poor prognosis association was particularly strong in normoxic tumor samples and was linked to an increased risk of distant metastasis. In vitro, only crosslink repair-defective HNSCC cell lines are highly migratory and invasive. This phenotype could also be induced in cells by inhibiting rad51 in repair competent and reduced by DNA-PK inhibition. In conclusion, DNA crosslink repair prediction expression profiles reveal a poor prognosis association in HNSCC. SIGNIFICANCE: This study uses innovative machine learning-based approaches to derive models that predict the effect of DNA repair defects on treatment outcome in HNSCC.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/21/5597/F1.large.jpg.
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Affiliation(s)
- Paul B M Essers
- Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Martijn van der Heijden
- Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.,Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Caroline V M Verhagen
- Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Emily M Ploeg
- Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Reinout H de Roest
- Department of Otolaryngology/Head and Neck Surgery, VUmc Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - C René Leemans
- Department of Otolaryngology/Head and Neck Surgery, VUmc Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Ruud H Brakenhoff
- Department of Otolaryngology/Head and Neck Surgery, VUmc Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Michiel W M van den Brekel
- Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Harry Bartelink
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Marcel Verheij
- Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.,Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Conchita Vens
- Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, the Netherlands. .,Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
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12
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Rolland V, Meyer F, Guitton MJ, Bussières R, Philippon D, Bairati I, Leclerc M, Côté M. A randomized controlled trial to test the efficacy of trans-tympanic injections of a sodium thiosulfate gel to prevent cisplatin-induced ototoxicity in patients with head and neck cancer. J Otolaryngol Head Neck Surg 2019; 48:4. [PMID: 30651130 PMCID: PMC6335693 DOI: 10.1186/s40463-019-0327-x] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2018] [Accepted: 01/07/2019] [Indexed: 12/12/2022] Open
Abstract
Background Cisplatin-induced hearing loss is frequent and severe. Antioxidants such as sodium thiosulfate (STS) can neutralize the effects of cisplatin. The objective of the trial was to test the efficacy of trans-tympanic injections of a STS gel to prevent cisplatin-induced ototoxicity. Methods Eligible participants were newly diagnosed patients with stage III or IV squamous cell carcinoma of the mouth, oropharynx, hypopharynx, or larynx and scheduled to be treated by concurrent chemoradiation (CCR). Patients with asymmetric hearing were not eligible. The planed treatment included cisplatin 100 mg/m2 at days 1, 22 and 43. A baseline pre-treatment complete audiometric evaluation (pure tone at frequencies ranging from 0.5 to 14 kHz, bone conduction at 0.5–4 kHz and DPOAEs) was performed. Adverse effects were noted according to CTCAE. On the day before the beginning of CCR, eligible and consenting patients were randomized to receive a trans-tympanic injection of the gel either in the left ear or in the right ear. A final post-treatment complete audiometric evaluation was scheduled to be performed 1 month after the end of CCR by audiologists kept blind to the ear assignment. For the main outcome, the permanent threshold shift (PTS) in decibel (dB) was calculated as the difference between the final and baseline measures at all pure tone frequencies at 0.5–14 kHz for each patient and for each ear. The main outcome was assessed blindly in a mixed linear model with the PTS as the dependent variable and intervention, frequency, their interaction and radiation dose to the cochlea as independent variables. Results Between January 2015 and April 2016, 13 patients were randomized. The trial was stopped in June 2016 for poor accrual. The average loss of hearing over all frequencies was 1.3 dB less for treated ears compared to control ears. Although not statistically (p = 0.61) nor clinically significant, the difference was in favor of the treated ears for all frequencies between 3 and 10 kHz. Conclusions Our trial suggests that STS deposited on the round window was safe for the middle and inner ears. More work is needed to improve the efficacy of trans-tympanic injections of cisplatin antidotes. Trial registration ClinicalTrials.gov, NTC02281006, Registered 3 November 2014.
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Affiliation(s)
- Viannique Rolland
- Department of Ophthalmology and Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Laval University, Pavillon Ferdinand-Vandry, Bureau 4889, 1050, avenue de la Médecine, Québec City, QC, G1V A06, Canada.,Centre Hospitalier Universitaire de Québec, Hôtel-Dieu de Québec, Quebec City, QC, Canada
| | - François Meyer
- Department of Social and Preventive Medicine, Faculty of Medicine, Laval University, Quebec City, QC, Canada.,Laval University Cancer Research Center, Quebec City, Canada
| | - Matthieu J Guitton
- Department of Ophthalmology and Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Laval University, Pavillon Ferdinand-Vandry, Bureau 4889, 1050, avenue de la Médecine, Québec City, QC, G1V A06, Canada.,CERVO Brain Research Center, Quebec City, QC, Canada
| | - Richard Bussières
- Department of Ophthalmology and Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Laval University, Pavillon Ferdinand-Vandry, Bureau 4889, 1050, avenue de la Médecine, Québec City, QC, G1V A06, Canada.,Centre Hospitalier Universitaire de Québec, Hôtel-Dieu de Québec, Quebec City, QC, Canada
| | - Daniel Philippon
- Department of Ophthalmology and Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Laval University, Pavillon Ferdinand-Vandry, Bureau 4889, 1050, avenue de la Médecine, Québec City, QC, G1V A06, Canada.,Centre Hospitalier Universitaire de Québec, Hôtel-Dieu de Québec, Quebec City, QC, Canada
| | - Isabelle Bairati
- Laval University Cancer Research Center, Quebec City, Canada.,Department of Surgery, Faculty of Medicine, Laval University, Quebec City, QC, Canada
| | - Mathieu Leclerc
- Department of Ophthalmology and Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Laval University, Pavillon Ferdinand-Vandry, Bureau 4889, 1050, avenue de la Médecine, Québec City, QC, G1V A06, Canada.,Department of Medicine, Faculty of Medicine, Laval University, Quebec City, QC, Canada
| | - Mathieu Côté
- Department of Ophthalmology and Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Laval University, Pavillon Ferdinand-Vandry, Bureau 4889, 1050, avenue de la Médecine, Québec City, QC, G1V A06, Canada. .,Centre Hospitalier Universitaire de Québec, Hôtel-Dieu de Québec, Quebec City, QC, Canada.
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13
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Eder-Czembirek C, Rechinger S, Kornek G, Selzer E, Seemann R. Experience in Intra-arterial Chemotherapy using Two Protocols for the Treatment of OSCC over Two Decades at the University Hospital Vienna. Clinics (Sao Paulo) 2018; 73:e433. [PMID: 30365825 PMCID: PMC6178862 DOI: 10.6061/clinics/2018/e433] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Accepted: 04/27/2018] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVES This retrospective study performed a comprehensive analysis of the usage of intra-arterial chemotherapy (iaCh) for locally recurrent UICC stage IV oral squamous cell carcinoma (OSCC) over two decades at the Department of Cranio-Maxillofacial and Oral Surgery at the University Hospital Vienna to assess the utility of its future use. METHODS Between 1994 and 2014, iaCh was indicated in 48 OSCC cases. In these, the two most frequent iaCh schemes, cisplatin/5-fluorouracil (Cis/5-FU) and methotrexate/bleomycin (MTX/Bleo), were chosen for further analysis. The effect on survival of two distinct intra-arterial protocols and their covariates were analyzed with the Kaplan-Meier method as well as univariate and multivariate Cox proportional hazard regression models. RESULTS The mean follow-up period was 29.91 months. The two intra-arterial chemotherapy groups did not differ significantly in sample size, demographic data or therapeutic covariates. The Cis/5-FU iaCh regimen was associated with significantly better overall survival (median OS 2.6 years vs. 1.3 years; p=0.002) and had a beneficial effect on survival (HR=3.62, p=0.015). Side effects occurred at a frequency similar to that described in the literature for intravenous chemotherapy (ivCh). CONCLUSIONS These results suggest a preference for administering Cis/5-FU for iaCh. Nevertheless, due to economic considerations in healthcare expenditures, there is no future for iaCh in the treatment of head and neck carcinomas because ivCh is known to be equivalent.
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Affiliation(s)
- Christina Eder-Czembirek
- Department of Cranio, Maxillofacial and Oral Surgery, Medical University Vienna, Vienna, Austria
- *Corresponding author. E-mail:
| | | | - Gabriela Kornek
- University Clinic of Internal Medicine, Department of Oncology, Medical University Vienna, Vienna, Austria
| | - Edgar Selzer
- University Clinic of Radiotherapy, Medical University Vienna, Vienna, Austria
| | - Rudolf Seemann
- Department of Cranio, Maxillofacial and Oral Surgery, Medical University Vienna, Vienna, Austria
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14
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Kraaijenga SAC, Oskam IM, van der Molen L, Hamming-Vrieze O, Hilgers FJM, van den Brekel MWM. Evaluation of long term (10-years+) dysphagia and trismus in patients treated with concurrent chemo-radiotherapy for advanced head and neck cancer. Oral Oncol 2015; 51:787-94. [PMID: 26027851 DOI: 10.1016/j.oraloncology.2015.05.003] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Revised: 05/07/2015] [Accepted: 05/11/2015] [Indexed: 10/23/2022]
Abstract
OBJECTIVES Assessment of long term (10-years+) swallowing function, mouth opening, and quality of life (QoL) in head and neck cancer (HNC) patients treated with chemo-radiotherapy (CRT) for advanced stage IV disease. MATERIALS AND METHODS Twenty-two disease-free survivors, participating in a multicenter randomized clinical trial for inoperable HNC (1999-2004), were evaluated to assess long-term morbidity. The prospective assessment protocol consisted of videofluoroscopy (VFS) for obtaining Penetration Aspiration Scale (PAS) and presence of residue scores, Functional Oral Intake Scale (FOIS) scores, maximum mouth opening measurements, and (SWAL-QOL and study-specific) questionnaires. RESULTS At a median follow-up of 11-years, 22 patients were evaluable for analysis. Ten patients (46%) were able to consume a normal oral diet without restrictions (FOIS score 7), whereas 12 patients (54%) had moderate to serious swallowing issues, of whom 3 (14%) were feeding tube dependent. VFS evaluation showed 15/22 patients (68%) with penetration and/or aspiration (PAS⩾3). Fifty-five percent of patients (12/22) had developed trismus (mouth opening⩽35mm), which was significantly associated with aspiration (p=.011). Subjective swallowing function (SWAL-QOL score) was impaired across almost all QoL domains in the majority of patients. Patients treated with IMRT showed significantly less aspiration (p=.011), less trismus (p=.035), and less subjective swallowing problems than those treated with conventional radiotherapy. CONCLUSION Functional swallowing and mouth opening problems are substantial in this patient cohort more than 10-years after organ-preservation CRT. Patients treated with IMRT had less impairment than those treated with conventional radiotherapy.
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Affiliation(s)
- S A C Kraaijenga
- The Netherlands Cancer Institute, Department of Head and Neck Oncology and Surgery, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
| | - I M Oskam
- The Netherlands Cancer Institute, Department of Head and Neck Oncology and Surgery, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
| | - L van der Molen
- The Netherlands Cancer Institute, Department of Head and Neck Oncology and Surgery, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
| | - O Hamming-Vrieze
- The Netherlands Cancer Institute, Department of Radiation Oncology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
| | - F J M Hilgers
- The Netherlands Cancer Institute, Department of Head and Neck Oncology and Surgery, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Institute of Phonetic Sciences/ACLC, University of Amsterdam, Spuistraat 210, 1012 VT Amsterdam, The Netherlands.
| | - M W M van den Brekel
- The Netherlands Cancer Institute, Department of Head and Neck Oncology and Surgery, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Institute of Phonetic Sciences/ACLC, University of Amsterdam, Spuistraat 210, 1012 VT Amsterdam, The Netherlands; Academic Medical Center, Department of Oral and Maxillofacial Surgery, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands
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15
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Noticewala SS, Mell LK, Olson SE, Read W. Survival in unresectable sinonasal undifferentiated carcinoma treated with concurrent intra-arterial cisplatin and radiation. World J Clin Cases 2015; 3:191-195. [PMID: 25685767 PMCID: PMC4317614 DOI: 10.12998/wjcc.v3.i2.191] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Revised: 11/02/2014] [Accepted: 11/19/2014] [Indexed: 02/05/2023] Open
Abstract
We report the successful use of RADPLAT to treat a patient with an unresectable T4N0 sinonasal undifferentiated carcinoma. This patient received 4 cycles of weekly intra-arterial cisplatin together with thiosulfate infusion with concurrent radiation therapy. Radiation therapy was given in 28 daily fractions to 54 Gy using intensity-modulated radiation therapy followed by a hypofractionated stereotactic boost of 3 fractions to 13 Gy to a total dose of 67 Gy in 31 fractions to the nasal sinus and bilateral neck. Intra-arterial cisplatin was administered using a bilateral approach due to the midline site of this tumor. Within days of the first intra-arterial cisplatin, there was an obvious decrease in tumor size. She has been followed with magnetic resonance imaging and positron emission tomography, and remains disease-free 47 mo post-treatment. Centers with expertise in intra-arterial chemotherapy could consider the RADPLAT approach for patients with unresectable sinonasal undifferentiated carcinoma.
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16
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Sun Y, Yu XL, Zhang GS, Liu YM, Tao CJ, Guo R, Tang LL, Zhang R, Guo Y, Ma J. Reduction of clinical target volume in patients with lateralized cancer of the nasopharynx and without contralateral lymph node metastasis receiving intensity-modulated radiotherapy. Head Neck 2015; 38 Suppl 1:E468-72. [PMID: 25677692 DOI: 10.1002/hed.24020] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2013] [Revised: 12/29/2014] [Accepted: 02/06/2015] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND This study investigated lymph node distribution in patients with lateralized cancer of the nasopharynx to identify areas suitable for clinical target volume (CTV) reduction. METHODS A total of 1680 patients with nasopharyngeal carcinoma (NPC) whose tumor involvement was assessed by MRI were reviewed retrospectively. RESULTS One hundred and twelve patients (7%) had a lateralized primary lesion. Of these, 9 patients (8%) had contralateral lymph nodes including 4 (4%) who had contralateral cervical lymph nodes (CLNs). The rates of contralateral level III/Va metastasis were <1% (1 of 104) and 12.5% (1 of 8) in patients without and with contralateral retropharynx/level II involvement, respectively. No known risk factors were significantly associated with contralateral lymph node metastasis. CONCLUSION Reduced cervical CTV coverage, including the contralateral level II, is feasible in patients with lateralized primary NPC, which may help to better protect the cervical OAR, including the thyroid, larynx, and esophagus. © 2015 Wiley Periodicals, Inc. Head Neck 38: E468-E472, 2016.
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Affiliation(s)
- Ying Sun
- State Key Laboratory of Oncology in Southern China, Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Xiao-Li Yu
- Department of Radiation Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Guang-Shun Zhang
- State Key Laboratory of Oncology in Southern China, Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Yi-Min Liu
- Department of Radiation Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Chang-Juan Tao
- State Key Laboratory of Oncology in Southern China, Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Rui Guo
- State Key Laboratory of Oncology in Southern China, Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Ling-Long Tang
- State Key Laboratory of Oncology in Southern China, Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Rong Zhang
- Imaging Diagnosis and Interventional Center, State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Ying Guo
- Department of Medical Statistics and Epidemiology, State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Jun Ma
- State Key Laboratory of Oncology in Southern China, Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, People's Republic of China
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17
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Kashiwagi N, Fujii T, Nishiyama K, Nakanishi K, Tomiyama N, Yagyu Y, Tsurusaki M, Kitano M, Murakami T. Superselective intra-arterial chemotherapy with concurrent radiotherapy for advanced parotid squamous cell carcinoma: a case report. Jpn J Clin Oncol 2015; 45:378-80. [DOI: 10.1093/jjco/hyu227] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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18
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Yunaiyama D, Saito K, Funatsu T, Nakayama H, Shimizu A, Ito H, Suzuki M, Akata S, Tokuuye K. Effectiveness of CT assists for intraarterial chemotherapy: therapeutic outcome of chemoradiation for advanced head and neck cancer extending across the anatomical midline. Jpn J Radiol 2014; 32:708-15. [PMID: 25380786 DOI: 10.1007/s11604-014-0370-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2014] [Accepted: 10/27/2014] [Indexed: 12/01/2022]
Abstract
OBJECTIVE The purpose of this study was to evaluate the effectiveness of CT assist for intraarterial chemotherapy in relation to the therapeutic outcomes of intraarterial chemoradiation for advanced head and neck cancer with extension across the anatomical midline (EAM). METHODS This retrospective study evaluated 64 consecutive patients. In total, 26 and 38 patients had cancer with or without EAM, respectively. These patients underwent an intraarterial cisplatin infusion (200 mg/m(2), days 1 and 35) and intravenous 5-FU infusion (800 mg/m(2), days 1-5 and 36-39) concomitantly with radiotherapy. Angiography-assisted CT was performed to confirm complete coverage during the intraarterial chemotherapy. The accuracy of diagnosing tumor vessels by digital subtraction angiography (DSA) was evaluated using receiver-operating characteristic analysis by two radiologists. The overall survival and locoregional control rates were calculated by the Kaplan-Meier method. RESULTS DSA was not useful for diagnosing tumor vessels. The 2-year overall survival rates for the patients with cancer with or without EAM were 83 and 90 %, while the 2-year locoregional control rates were 95 and 82 %, respectively. Locoregional control or the overall survival rates showed no significant differences. CONCLUSIONS Intraarterial chemotherapy using angiography-assisted CT during chemoradiation therapy can achieve comparable therapeutic outcomes for cancer with and without EAM.
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Affiliation(s)
- Daisuke Yunaiyama
- Department of Radiology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
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Fraser JF, Hussain MS, Eskey C, Abruzzo T, Bulsara K, English J, Blackham K, Do HM, Prestigiacomo C, Jayaraman MV, Patsalides A, Kelly M, Sunshine JL, Meyers P. Reporting standards for endovascular chemotherapy of head, neck and CNS tumors. J Neurointerv Surg 2013; 5:396-9. [PMID: 23828325 DOI: 10.1136/neurintsurg-2013-010841] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
BACKGROUND The goal of this article is to provide expert consensus recommendations for reporting standards, terminology and definitions when reporting on neurointerventional chemotherapy administration for head and neck tumors. These criteria may be used to design clinical trials, to provide definitions for patient stratification and to permit robust analysis of published data. METHODS This publication represents a consensus document by the Society for Neurointerventional Surgery. A PubMed search was conducted and included articles published in 2002-2011, with the search strategy designed to identify all studies of intra-arterial chemotherapy for tumors of neck and head. Articles were evaluated for evidence class, and recommendations were made using guidelines for evidence-based medicine proposed by a joint committee of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. Specifically, technical methods, outcome variables and reported complications were highlighted. RESULTS Thirty-five publications were included in the review. While most studies represent class III evidence, there was sufficient concordance to justify level 2 recommendations regarding technical methods for administration of intra-arterial chemotherapy. The data also support level 2 recommendations regarding reporting of particular outcome variables subsumed within broad categories entitled 'Procedure-related', 'Disease control' and 'Survival'. The data support recommendations for the reporting of access site-related, neurologic, head and neck, ocular, hematologic and systemic complications, and also complications related to the percutaneous access site. CONCLUSIONS Intra-arterial chemotherapy is a growing field in interventional neuroradiology. It is important to adopt uniform technical and reporting standards that will allow cross-publication comparisons and facilitate homogeneous practice standards. Published data support such standards, which are vital for the consistent evaluation of future published research.
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Affiliation(s)
- Justin F Fraser
- Department of Neurological Surgery, University of Kentucky, Lexington, KY, USA
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Lee MH, Kim SU, Kim DY, Ahn SH, Choi EH, Lee KH, Lee DY, Seong J, Han KH, Chon CY, Park JY. Early on-treatment predictions of clinical outcomes using alpha-fetoprotein and des-gamma-carboxy prothrombin responses in patients with advanced hepatocellular carcinoma. J Gastroenterol Hepatol 2012; 27:313-322. [PMID: 21793906 DOI: 10.1111/j.1440-1746.2011.06867.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM The clinical utility of alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) as a predictor of treatment outcome in patients with advanced hepatocellular carcinoma (HCC) receiving hepatic artery infusional chemotherapy (HAIC) or concurrent chemoradiation therapy (CCRT) has been poorly defined. METHODS Between January 2003 and December 2007, we enrolled 127 treatment-naïve patients who received HAIC (n = 60) or CCRT (n = 67) as an initial treatment modality. An AFP or DCP response was defined as a reduction of more than 20% from the baseline level. RESULTS AFP responders showed significantly better overall survival (OS) than non-responders among patients with HAIC (median 17.3 vs 6.4 months, P < 0.001) and with CCRT (median 17.6 vs 8.7 months, P = 0.014). DCP responders in the CCRT group also showed significantly better progression-free survival (PFS) than non-responders (median 9.2 vs 3.1 months, P < 0.001). Multivariate Cox regression analyses showed that AFP response was independently predictive of OS in both groups (P = 0.009 in HAIC and P = 0.008 in CCRT) whereas DCP only predicted PFS in patients with CCRT (P = 0.015). CONCLUSIONS Early on-treatment AFP response was predictive of OS in treatment-naïve patients with advanced HCC receiving HAIC and CCRT as an initial treatment modality. Furthermore, DCP response was useful for predicting PFS in patients with CCRT.
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Affiliation(s)
- Myoung Ha Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Nakamura T, Fuwa N, Takayama K, Inokuchi H, Tomoda T, Takada A, Makita C, Shiomi M, Yokouchi JI, Watanabe K. Phase I study of weekly docetaxel and cisplatin arterial infusion for recurrent head and neck cancer. Head Neck 2011; 34:1634-9. [PMID: 22179897 DOI: 10.1002/hed.21983] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/08/2011] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND We planned a phase I study of weekly arterial infusion of docetaxel and cisplatin via a superficial temporal artery for recurrent head and neck cancer to determine the optimal dose. METHODS The dose of cisplatin was fixed and the dose of docetaxel was escalated from 8 mg/m(2) , with an increase of 2 mg/m(2) per step, to identify the maximum tolerated dose (MTD). In total, 4 courses of weekly chemotherapy were administered. RESULTS Twelve patients were recruited to this trial. The MTD of docetaxel was 14 mg/m(2) . At this dose level, dose-limiting toxicity was observed in 2 of 3 patients. One patient experienced grade 3 leukopenia, while the other experienced grade 3 leukopenia. Myelosuppression was the dose-limiting toxicity for this regimen. CONCLUSION The recommended dose for weekly arterial infusion of docetaxel was identified as 12 mg/m(2) combined with weekly cisplatin at 40 mg/m(2) , with 4 courses of each.
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Affiliation(s)
- Tatsuya Nakamura
- Department of Radiation Oncology, Southern Tohoku Proton Therapy Center, 7-172 Yatsuyamada, Koriyama, Fukushima 963-8052, Japan.
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22
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Ackerstaff AH, Rasch CRN, Balm AJM, de Boer JP, Wiggenraad R, Rietveld DHF, Gregor RT, Kröger R, Hauptmann M, Vincent A, Hilgers FJM. Five-year quality of life results of the randomized clinical phase III (RADPLAT) trial, comparing concomitant intra-arterial versus intravenous chemoradiotherapy in locally advanced head and neck cancer. Head Neck 2011; 34:974-80. [DOI: 10.1002/hed.21851] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2010] [Revised: 04/08/2011] [Accepted: 05/19/2011] [Indexed: 11/12/2022] Open
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Knegjens JL, Hauptmann M, Pameijer FA, Balm AJ, Hoebers FJ, de Bois JA, Kaanders JH, van Herpen CM, Verhoef CG, Wijers OB, Wiggenraad RG, Buter J, Rasch CR. Tumor volume as prognostic factor in chemoradiation for advanced head and neck cancer. Head Neck 2011; 33:375-82. [PMID: 20629076 DOI: 10.1002/hed.21459] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND Tumor volume is an important predictor of outcome in radiotherapy alone. Its significance in concomitant chemoradiation (CCRT) is much less clear. We analyzed the prognostic value of primary tumor volume for advanced head and neck squamous cell carcinoma (HNSCC) treated with CCRT. METHODS Three hundred sixty patients treated with definitive CCRT for advanced HNSCC were selected. The pretreatment MRI or CT scan was used to calculate the primary tumor volume. Median follow-up was 19.8 months. RESULTS The average primary tumor volume was 37.0 cm³ (range, 2.1-182.7 cm³; median, 28.7 cm³). Multivariate analysis showed a significant effect of tumor volume on local control. The hazard ratio for a local recurrence increased by 14% per 10 cm³ volume increase (95% CI, 8% to 21%). There was no significant independent effect of T and N status on local control. CONCLUSION For advanced HNSCC, tumor volume is more powerful for predicting outcome after CCRT than TNM status.
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Affiliation(s)
- Joost L Knegjens
- Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
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Organ Preservation With Daily Concurrent Chemoradiotherapy Using Superselective Intra-Arterial Infusion via a Superficial Temporal Artery for T3 and T4 Head and Neck Cancer. Int J Radiat Oncol Biol Phys 2011; 79:1428-35. [DOI: 10.1016/j.ijrobp.2010.01.011] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2009] [Revised: 11/21/2009] [Accepted: 01/02/2010] [Indexed: 11/18/2022]
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Yu KH, Yu SCH, Hui EP, Kam MKM, Vlantis AC, Yuen E, Chan ATC. Accelerated fractionation radiotherapy and late intensification with 2 intra-arterial cisplatin infusions for locally advanced head and neck squamous cell carcinoma. Head Neck 2010; 32:913-20. [PMID: 19885925 DOI: 10.1002/hed.21279] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND This study was established to determine the maximum tolerated dose of intra-arterial cisplatin (IAC) concurrent with accelerated fractionation radiotherapy for locally advanced head and neck squamous cell carcinoma (HNSCC). METHODS We conducted a phase I study. Treatment consisted of 70 Gy/35 fractions/5.8 weeks and 2 weekly IAC infusions during the last 2 weeks. RESULTS Ten patients were recruited. Two patients had stage III, 1 had stage IVa, and 7 had stage IVb disease. Three patients received IAC at 100 mg/m(2), 3 at 125 mg/m(2), and 4 at 150 mg/m(2). Nine patients received both planned infusions. Dose-limiting toxicity occurred at 150 mg/m(2) as transient grade 4 leukopenia and prolonged grade 3 acute skin reactions. The maximum tolerated dose was 125 mg/m(2). Six patients survived disease-free at 39 to 67 months. CONCLUSIONS It was feasible to give IAC concurrent with accelerated fractionation radiotherapy for locally advanced HNSCC. The maximum tolerated dose of cisplatin was 125 mg/m(2).
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Affiliation(s)
- Kwok Hung Yu
- Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
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Rasch CRN, Hauptmann M, Schornagel J, Wijers O, Buter J, Gregor T, Wiggenraad R, de Boer JP, Ackerstaff AH, Kroger R, Hoebers FJP, Balm AJM, Hilgers FJ. Intra-arterial versus intravenous chemoradiation for advanced head and neck cancer: Results of a randomized phase 3 trial. Cancer 2010; 116:2159-65. [PMID: 20187094 DOI: 10.1002/cncr.24916] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND Chemoradiation is the preferred treatment for advanced stage IV head and neck cancer. Higher doses of chemotherapy yielded promising results in vitro and vivo, confirmed by intra-arterial (IA) cisplatin-based chemoradiation in phase 2 studies. METHODS Two hundred and thirty-nine patients with (functionally) unresectable head and neck cancer were included, from 2000 to 2004, in a multicenter, randomized phase 3 trial, comparing IA and intravenous chemoradiation. Intravenous chemoradiation comprised 3x100 mg/m(2) cisplatin infusion on Days 1, 22, 43 combined with 70 Gy in 35 daily fractions. The IA chemoradiation treatment arm comprised 4x150 mg/m(2) cisplatin administered in the tumor-feeding artery on Days 1, 8, 15, 22, immediately followed by systemic rescue with sodium thiosulfate with the same radiotherapeutic regimen. RESULTS Two patients were excluded from analysis because of nontreatment-related death immediately after randomization (n = 1) and esophageal carcinoma (n = 1). The median follow-up was 33 months 1-104 months. Ninety percent of the patients required tube feeding during treatment. Renal toxicity >grade 2 was 9% in the intravenous compared with 1% in the IA treatment arm (P <or= .0001). There was no difference in locoregional control, disease-free survival (DFS) or overall survival (OS), between the treatment arms. At 3 years, local control, locoregional control, DFS, and OS was .76, .63, .44, .51 in the IA versus .70, .65, .47, .47 in the intravenous treatment arm, respectively. CONCLUSIONS Cisplatin-based IA chemoradiation was not superior to intravenous chemoradiation for advanced stage IV head and neck cancer regarding locoregional control and survival.
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Affiliation(s)
- Coen R N Rasch
- Department of Radiation Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoekhuis, Amsterdam, Netherlands.
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Robbins KT, Howell SB, Williams JS. Intra-arterial chemotherapy for head and neck cancer: is there a verdict? Cancer 2010; 116:2068-70. [PMID: 20186833 DOI: 10.1002/cncr.24930] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Lee YJ, Lee CG, Cho BC, Kim GE, Choi HJ, Choi EC, Sohn JH, Kim JH. Weekly 5-fluorouracil plus cisplatin for concurrent chemoradiotherapy in patients with locally advanced head and neck cancer. Head Neck 2010; 32:235-43. [PMID: 19572288 DOI: 10.1002/hed.21177] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND In locally advanced head and neck cancer, concurrent chemoradiotherapy (CRT) with combined 5-fluorouracil (5-FU) and cisplatin has increased acute toxicities as well as survival. Once-weekly chemotherapeutic administration schedule may reduce severe toxicities. Thus, we investigated CRT using weekly administration of 5-FU-cisplatin in locally advanced head and neck cancer. METHODS In a single-arm, phase II study, CRT included radiation (70.0 Gy/35 fr) and weekly 5-FU (750 mg/m2) and cisplatin (20 mg/m2). RESULTS Thirty-two patients completed planned radiation. Thirteen (41%) achieved complete response, and 16 (50%) partial response. Twelve patients (38%) experienced acute grade 3 toxicities. Grade 3 mucositis, which was the most common toxicity, developed in 5 (16%) patients. The survival rates at 1 and 2 years were 81% and 76%, respectively. The progression-free survival rates at 1 and 2 years were 69% and 66%, respectively. CONCLUSIONS We demonstrated weekly 5-FU-cisplatin with conventional radiotherapy was efficacious and feasible with high compliance rate in locally advanced head and neck cancer.
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Affiliation(s)
- Young Joo Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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29
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[Analyses of the results in the treatment of locally advanced hypopharyngeal carcinoma with different therapeutic approach]. ACTA ACUST UNITED AC 2009; 56:35-40. [PMID: 19504987 DOI: 10.2298/aci0901035m] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
INTRODUCTION treatment of locoregional advanced hypopharyngeal cancers of grades III and IV would be surgery and/or radiotherapy. An increasing number of authors has emphasized favorable effects of neoadjuvant chemotherapy and radiotherapy with potentiation. THE AIM the authors presented therapeutical results of three-year survived patients with squamocellular cancers of the hypopharynx (SCC Hy), grades III and IV, in relation to specific modalities of therapeutical approach. METHODS a series of 207 patients with grades III and IV of SCC Hy, treated in the period 1982 to 2002, was analyzed. Group I consisted of 131 patients who had surgery and postoperative radiotherapy (SUR-RT). Group II included 16 patients who underwent induction chemotherapy, surgery and postoperative radiotherapy (IC-SUR-RT). Group III consisted of 60 patients, who had primary radiotherapy (RT). Group IV involved 29 patients who were treated, in the period 2003-2006, by neoadjuvant chemotherapy followed by radiotherapy with potentiation (CHT-RT). RESULTS three-year survival in Group I was 67.94%, Group II--50%, Group III--30%, and in Group IV was 51.72%. Five-year survival was analyzed only in group I-III. The longest survival was observed in Group I--33.59%. CONCLUSION the best therapeutical results were achieved in patient group that was primarily operated on and then had postoperative radiotherapy, while the worst survival was recorded in patients who had primary radiotherapy.
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van der Putten L, van den Broek GB, de Bree R, van den Brekel MWM, Balm AJM, Hoebers FJP, Doornaert P, Leemans CR, Rasch CRN. Effectiveness of salvage selective and modified radical neck dissection for regional pathologic lymphadenopathy after chemoradiation. Head Neck 2009; 31:593-603. [PMID: 19132716 DOI: 10.1002/hed.20987] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Affiliation(s)
- Lisa van der Putten
- Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute-Antoni Van Leeuwenhoek Hospital, Amsterdam, The Netherlands
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van den Broek GB, Wildeman M, Rasch CRN, Armstrong N, Schuuring E, Begg AC, Looijenga LHJ, Scheper R, van der Wal JE, Menkema L, van Diest PJ, Balm AJM, van Velthuysen MLF, van den Brekel MWM. Molecular markers predict outcome in squamous cell carcinoma of the head and neck after concomitant cisplatin-based chemoradiation. Int J Cancer 2009; 124:2643-50. [PMID: 19253368 DOI: 10.1002/ijc.24254] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Not all patients with squamous cell carcinomas of the head and neck (HNSCC) benefit from concurrent cisplatin-based chemoradiation, but reliable predictive markers for outcome after chemoradiation are scarce. We have investigated potential prognostic biomarkers for outcome in a large group of patients. Ninety-one tumor biopsies taken from consecutive HNSCC patients were evaluated for protein expression on a tissue microarray. Using immunohistochemistry, 18 biomarkers, involved in various cellular pathways were investigated. Univariable and multivariable proportional hazard analyses were performed to investigate associations between each individual marker and outcome. In addition, the global test was used to test all variables simultaneously and selected combinations of markers for an overall association with local control. Univariable analysis showed statistically significant increased relative risks of RB, P16 and MRP2 for local control and MDR1 and HIF-1alpha for overall survival. MRP2, MDR1 and P16 levels were positively associated with outcome whereas RB and HIF-1alpha had a negative relationship. Using Goeman's global testing no combination of markers was identified that was associated with local control. Grouping the markers according to their function revealed an association between a combination of 3 markers (P16, P21 and P27) and outcome (p = 0.05) was found. In the multivariable analysis, MRP2 and RB remained significant independent predictive markers for local control. This study describes the prognostic value of biomarkers for the outcome in patients uniformly treated with concurrent chemoradiation. MRP2 and RB were found to be associated with outcome in patients treated with concurrent chemoradiation.
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Affiliation(s)
- Guido B van den Broek
- Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
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Relative Contributions of Radiation and Cisplatin-Based Chemotherapy to Sensorineural Hearing Loss in Head-and-Neck Cancer Patients. Int J Radiat Oncol Biol Phys 2009; 73:779-88. [DOI: 10.1016/j.ijrobp.2008.05.040] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2007] [Revised: 05/06/2008] [Accepted: 05/07/2008] [Indexed: 11/15/2022]
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Ackerstaff AH, Balm AJM, Rasch CRN, de Boer JP, Wiggenraad R, Rietveld DHF, Gregor RT, Kröger R, Hilgers FJM. First-year quality of life assessment of an intra-arterial (RADPLAT) versus intravenous chemoradiation phase III trial. Head Neck 2009; 31:77-84. [DOI: 10.1002/hed.20937] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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Detection of locoregional recurrent head and neck cancer after (chemo)radiotherapy using modern imaging. Oral Oncol 2008; 45:386-93. [PMID: 19095487 DOI: 10.1016/j.oraloncology.2008.10.015] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
After radiotherapy with or without chemotherapy differentiation between residual and recurrent head and neck cancer and (chemo)radiation sequelae is often difficult. Currently, most physicians aggressively pursue potential recurrences, leading to a high rate of futile invasive diagnostic, e.g. examinations under general anaesthesia with taking of biopsies, and surgical procedures, e.g. planned neck dissections, and a waste of health care resources. Therefore, diagnostic techniques which reliably select patients who should undergo these procedures are warranted. Conventional imaging techniques are not reliable enough for this purpose. Potential imaging techniques to detect residual and recurrent locoregional disease after chemoradiation are (serial) CT or MRI and FDG-PET, eventually in combination with specific response criteria or scoring systems. Diffusion MRI and PET/CT may further improve these techniques. FDG-PET may help to select patients clinically suspected of recurrent laryngeal carcinoma after radiotherapy for direct laryngoscopy under general anaesthesia. It is not yet clear whether FDG-PET can reliable avoid futile routine evaluation by examination under general anaesthesia in oral and oropharyngeal cancer and planned neck dissection when a residual mass persists in the neck after (chemo)radiation. The most reliable scoring criteria and the optimal time interval between completion of radiation and FDG-PET still has to be assessed.
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van der Molen L, van Rossum MA, Burkhead LM, Smeele LE, Hilgers FJM. Functional outcomes and rehabilitation strategies in patients treated with chemoradiotherapy for advanced head and neck cancer: a systematic review. Eur Arch Otorhinolaryngol 2008; 266:889-900. [DOI: 10.1007/s00405-008-0817-3] [Citation(s) in RCA: 96] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2008] [Accepted: 08/11/2008] [Indexed: 01/23/2023]
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Han KH, Seong J, Kim JK, Ahn SH, Lee DY, Chon CY. Pilot clinical trial of localized concurrent chemoradiation therapy for locally advanced hepatocellular carcinoma with portal vein thrombosis. Cancer 2008; 113:995-1003. [PMID: 18615601 DOI: 10.1002/cncr.23684] [Citation(s) in RCA: 123] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Patients with advanced hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) have a particularly grave prognosis. In the current study, an attempt was made to localize chemoradiation therapy (CCRT) followed by hepatic arterial infusion chemotherapy (HAIC) in patients with locally advanced HCC with PVT and good reserve liver function. The objective of the current study was to evaluate the therapeutic effect of localized CCRT followed by HAIC as a new treatment modality for these patients. METHODS Between January 1998 and December 2003, 40 patients were recruited. Concurrent regional chemotherapy using an intra-arterial implanted port plus localized external beam radiotherapy was performed with a total of 45 gray (Gy) over 5 weeks with conventional fractionation and hepatic arterial infusion of 5-fluorouracil (5-FU), which was administered during the first and fifth weeks of radiotherapy. One month after localized CCRT, HAIC with 5-FU and cisplatin was administered every 4 weeks. RESULTS One month after localized CCRT, an objective response was observed on the intention-to-treat analysis in 18 of 40 patients (45%). The actuarial 3-year overall survival rate was 24.1% and the median survival time was 13.1 months from the start of radiation treatment. Responders after localized CCRT demonstrated significantly better survival (P = .033) than nonresponders. CONCLUSIONS The substantial response rate as well as median survival time noted in the current study encourages the use of this new approach in patients with locally advanced HCC with PVT.
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Affiliation(s)
- Kwang-Hyub Han
- Department of Internal Medicine, Yonsei Liver Cancer Special Clinic, Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
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Gandhi D, Gemmete JJ, Ansari SA, Gujar SK, Mukherji SK. Interventional neuroradiology of the head and neck. AJNR Am J Neuroradiol 2008; 29:1806-15. [PMID: 18784215 DOI: 10.3174/ajnr.a1211] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Interventional neuroradiology procedures are a valuable asset in the diagnosis, treatment, and surgical management of various disorders affecting the extracranial head and neck. A detailed understanding of cross-sectional and vascular anatomy and an awareness of potential collateral pathways between extracranial and intracranial vessels are essential for ensuring safe and successful procedures. With the use of high-quality imaging and a meticulous technique, the incidence of major complications is extremely low.
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Affiliation(s)
- D Gandhi
- Division of Interventional Neuroradiology, University of Michigan Health System, Ann Arbor, Mich, USA.
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Fuwa N, Kodaira T, Furutani K, Tachibana H, Nakamura T, Nakahara R, Tomoda T, Inokuchi H, Daimon T. Intra-arterial chemoradiotherapy for locally advanced oral cavity cancer: analysis of therapeutic results in 134 cases. Br J Cancer 2008; 98:1039-45. [PMID: 18283309 PMCID: PMC2275486 DOI: 10.1038/sj.bjc.6604272] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
The objective of this study was to investigate the therapeutic results of arterial injection therapy via the superficial temporal artery for 134 cases of stages III and IV (M0) oral cavity cancer retrospectively, and to clarify the prognostic factors. We administered intra-arterial chemoradiotherapy by continuous infusion of carboplatin in 65 cases from January 1993 to July 2002. Systemic chemotherapy was performed on 26 cases at the same time. We administered intra-arterial chemoradiotherapy by cisplatin with sodium thiosulphate in 69 cases from October 2002 to December 2006. Systemic chemotherapy was performed on 48 cases at the same time. The 3-year local control rate was 68.6% (T2-3: 77.9%; T4: 51.3%), and the 3-year survival rate was 53.9% (stage III: 62.9%; stage IV: 45.3%). Regarding the results of multivariate analysis of survival rates, age (<65), selective intra-arterial infusion, and the use of cisplatin as an agent for intra-arterial infusion were significant factors. The therapeutic results of intra-arterial chemoradiotherapy via the superficial temporal artery were not inferior to the results of surgery. In particular, the results of arterial injection therapy by cisplatin with sodium thiosulphate were excellent, so we believe that it will be a new therapy for advanced oral cavity cancer.
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Affiliation(s)
- N Fuwa
- Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
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Doweck I, Robbins KT, Samant S, Vieira F. Intra-arterial chemoradiation for T3-4 oral cavity cancer: treatment outcomes in comparison to oropharyngeal and hypopharyngeal carcinoma. World J Surg Oncol 2008; 6:2. [PMID: 18194553 PMCID: PMC2254405 DOI: 10.1186/1477-7819-6-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2007] [Accepted: 01/14/2008] [Indexed: 11/30/2022] Open
Abstract
Background Surgery followed by radiotherapy is the standard of care for resectable locally advanced oral cavity squamous cell carcinoma (SCC). We report the treatment outcomes of patients with T3-T4 SCC of the oral cavity treated with chemoradiation, an alternative approach. Patients and methods From a series of 240 patients with stage III-IV carcinoma of the upper aerodigestive tract who were treated consecutively according to the RADPLAT protocol, a subset analysis of 155 patients with T3-T4 SCC (Oral cavity SCC N = 22, oropharynx SCC N = 94 and hypopharynx SCC N = 39), was performed. The goal was to test the hypothesis that oral cavity SCC treated with chemoradiation has similar outcomes to the two comparison sites. Results With a median follow-up of 58 months, local disease control was 69% and the overall survival was 37%. In comparison, local disease control for the oropharynx and hypopharynx groups was 86% and 79% respectively. The overall survival rate for the oropharyngeal and hypopharyngeal groups were 41% and 6% respectively Conclusion Patients with locally advanced oral cavity cancer treated with the chemoradiation protocol RADPLAT have outcomes that are equal or better compared to patients with similar disease involving the oropharynx and hypopharynx
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Affiliation(s)
- Ilana Doweck
- Department of Otolaryngology- Head and Neck Surgery, Carmel Medical Center, and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
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Fujishiro Y, Nakao K, Watanabe K, Ebihara Y, Nakamura N, Mori H, Hayashi N, Asakage T. A new aspect of tri-modal therapy with superselective intra-arterial chemotherapy in maxillary sinus carcinoma. Acta Otolaryngol 2007:151-6. [PMID: 18340587 DOI: 10.1080/03655230701599842] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
CONCLUSION This superselective intra-arterial intervention technique enabled us to administer a higher dose of cisplatinum to the local lesion with a lower incidence of adverse issues by use of neutralizer, compared with the conventional methods. OBJECTIVE A wide variety of modalities, including surgery, radiotherapy, and chemotherapy, alone or in combination, have been reported for the treatment of maxillary sinus cancer. However, there is still much controversy with regard to the optimum treatment to obtain better local control and acceptable preservation of shape and function. Since 2001, we have performed superselective intra-arterial infusion chemotherapy in combination with radiotherapy and surgery aiming at a higher local control rate. PATIENTS AND METHODS This was a review of prospective collected data. The therapeutic design consisted of weekly intra-arterial infusion of high dose CDDP with concomitant radiotherapy and planned surgery performed during chemo-radiation therapy. From June 2001 to January 2004, 14 patients with squamous cell carcinoma of maxillary sinus underwent this treatment procedure at the University of Tokyo Hospital. RESULTS The local response rate with this combined therapy was 85.7%. Overall survival rates at 1 and 2 years were 78.6% and 56.2%, respectively, with median follow-up of 25.5 months.
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Hoebers FJP, Kartachova M, de Bois J, van den Brekel MWM, van Tinteren H, van Herk M, Rasch CRN, Valdés Olmos RA, Verheij M. 99mTc Hynic-rh-Annexin V scintigraphy for in vivo imaging of apoptosis in patients with head and neck cancer treated with chemoradiotherapy. Eur J Nucl Med Mol Imaging 2007; 35:509-18. [PMID: 17994297 PMCID: PMC2275773 DOI: 10.1007/s00259-007-0624-x] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2007] [Accepted: 09/28/2007] [Indexed: 11/25/2022]
Abstract
Purpose The purpose of this study was to determine the value of 99mTc Hynic-rh-Annexin-V-Scintigraphy (TAVS), a non-invasive in vivo technique to demonstrate apoptosis in patients with head and neck squamous cell carcinoma. Methods TAVS were performed before and within 48 h after the first course of cisplatin-based chemoradiation. Radiation dose given to the tumour at the time of post-treatment TAVS was 6–8 Gy. Single-photon emission tomography data were co-registered to planning CT scan. Complete sets of these data were available for 13 patients. The radiation dose at post-treatment TAVS was calculated for several regions of interest (ROI): primary tumour, involved lymph nodes and salivary glands. Annexin uptake was determined in each ROI, and the difference between post-treatment and baseline TAVS represented the absolute Annexin uptake: Delta uptake (ΔU). Results In 24 of 26 parotid glands, treatment-induced Annexin uptake was observed. Mean ΔU was significantly correlated with the mean radiation dose given to the parotid glands (r = 0.59, p = 0.002): Glands that received higher doses showed more Annexin uptake. ΔU in primary tumour and pathological lymph nodes showed large inter-patient differences. A high correlation was observed on an inter-patient level (r = 0.71, p = 0.006) between the maximum ΔU in primary tumour and in the lymph nodes. Conclusions Within the dose range of 0–8 Gy, Annexin-V-scintigraphy showed a radiation-dose-dependent uptake in parotid glands, indicative of early apoptosis during treatment. The inter-individual spread in Annexin uptake in primary tumours could not be related to differences in dose or tumour volume, but the Annexin uptake in tumour and lymph nodes were closely correlated. This effect might represent a tumour-specific apoptotic response.
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Affiliation(s)
- Frank J P Hoebers
- Department of Radiotherapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, Amsterdam, The Netherlands,
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van den Broek GB, Wreesmann VB, van den Brekel MWM, Rasch CRN, Balm AJM, Rao PH. Genetic abnormalities associated with chemoradiation resistance of head and neck squamous cell carcinoma. Clin Cancer Res 2007; 13:4386-91. [PMID: 17671120 DOI: 10.1158/1078-0432.ccr-06-2817] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
PURPOSE To identify reliable predictors of chemoradiation resistance of advanced head and neck squamous cell carcinoma (HNSCC). EXPERIMENTAL DESIGN We did a matched-pair analysis of 20 chemoradiation-resistant and 20 sensitive HNSCCs, identified among a series of 104 consecutively treated cases. We compared the global DNA copy number profiles derived from comparative genomic hybridization analysis of both groups to identify genetic markers associated with chemoradiation resistance. RESULTS Although sensitive and resistant case groups were characterized by a similar total number of genetic aberrations, high-level amplifications were more frequent in resistant tumors. Resistant tumors were characterized by a different profile of genetic changes. Gains of 3q11-q13, 3q21-q26.1, and 6q22-q27 and losses of 3p11-pter and 4p11-pter were significantly associated with chemoradiation resistance. High-level amplifications unique to resistant cases involved the chromosomal regions 1p32, 3q24, 7p11.1, 7p11.2-12, 8p11.1, 8p11.1-12, 12q15, 13q21, 15q12, 18p11.3, and 18q11. CONCLUSIONS Sensitive and resistant HNSCCs are characterized by divergent genomic profiles. These profiles may be valuable as predictive markers of treatment failure.
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Affiliation(s)
- Guido B van den Broek
- Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
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Pramana J, Van den Brekel MWM, van Velthuysen MLF, Wessels LFA, Nuyten DS, Hofland I, Atsma D, Pimentel N, Hoebers FJP, Rasch CRN, Begg AC. Gene expression profiling to predict outcome after chemoradiation in head and neck cancer. Int J Radiat Oncol Biol Phys 2007; 69:1544-52. [PMID: 17931799 DOI: 10.1016/j.ijrobp.2007.08.032] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2007] [Revised: 08/07/2007] [Accepted: 08/07/2007] [Indexed: 12/21/2022]
Abstract
PURPOSE The goal of the present study was to improve prediction of outcome after chemoradiation in advanced head and neck cancer using gene expression analysis. MATERIALS AND METHODS We collected 92 biopsies from untreated head and neck cancer patients subsequently given cisplatin-based chemoradiation (RADPLAT) for advanced squamous cell carcinomas (HNSCC). After RNA extraction and labeling, we performed dye swap experiments using 35k oligo-microarrays. Supervised analyses were performed to create classifiers to predict locoregional control and disease recurrence. Published gene sets with prognostic value in other studies were also tested. RESULTS Using supervised classification on the whole series, gene sets separating good and poor outcome could be found for all end points. However, when splitting tumors into training and validation groups, no robust classifiers could be found. Using Gene Set Enrichment analysis, several gene sets were found to be enriched in locoregional recurrences, although with high false-discovery rates. Previously published signatures for radiosensitivity, hypoxia, proliferation, "wound," stem cells, and chromosomal instability were not significantly correlated with outcome. However, a recently published signature for HNSCC defining a "high-risk" group was shown to be predictive for locoregional control in our dataset. CONCLUSION Gene sets can be found with predictive potential for locoregional control after combined radiation and chemotherapy in HNSCC. How treatment-specific these gene sets are needs further study.
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Affiliation(s)
- Jimmy Pramana
- Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, the Netherlands
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Hoebers FJP, Heemsbergen W, Balm AJM, van Zanten M, Schornagel JH, Rasch CRN. Concurrent chemoradiation with daily low dose cisplatin for advanced stage head and neck carcinoma. Radiother Oncol 2007; 85:42-7. [PMID: 17445927 DOI: 10.1016/j.radonc.2007.03.014] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2006] [Revised: 03/20/2007] [Accepted: 03/22/2007] [Indexed: 11/28/2022]
Abstract
BACKGROUND AND PURPOSE To evaluate treatment results of concurrent chemoradiation with daily low dose cisplatin. MATERIALS AND METHODS 121 patients with advanced stage HNSCC were treated with RT (35 x 2 Gy) and cisplatin (6 mg/m(2) i.v. x20, daily before RT). After 47 patients, the treatment protocol (Standard Group) was changed: Daily i.v. prehydration and accelerated RT were given to the subsequent 74 patients (Hydr-Ac-RT Group). RESULTS Mean follow-up was 29 months (range 7-62). More chemotherapy could be administered in the Hydr-Ac-RT Group (maximum no. of 20 cisplatin-infusions increased from 59% to 91% of patients, p=0.008), with less renal toxicity (p<0.001) and less hospital admissions (p<0.02). However, mucositis was more pronounced and tubefeeding more frequent in the Hydr-Ac-RT Group. The CR rate of the primary tumor increased from 74% (Standard Group) to 90% (Hydr-Ac-RT Group) (p=0.06), although this did not lead to an improvement in loco-regional control. CONCLUSIONS Concurrent chemoradiation with daily low dose cisplatin is feasible and effective for selected patients with advanced HNSCC. Although the addition of accelerated RT resulted in more mucositis and tubefeeding, the introduction of prehydration led to better compliance to therapy with more chemotherapy administered and less hospital admissions.
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Affiliation(s)
- Frank J P Hoebers
- Department of Radiotherapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
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Zuur CL, Simis YJ, Lansdaal PE, Hart AA, Schornagel JH, Dreschler WA, Rasch CR, Balm AJ. Ototoxicity in a Randomized Phase III Trial of Intra-Arterial Compared With Intravenous Cisplatin Chemoradiation in Patients With Locally Advanced Head and Neck Cancer. J Clin Oncol 2007; 25:3759-65. [PMID: 17704425 DOI: 10.1200/jco.2006.08.9540] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Purpose Cisplatin concomitantly administered with radiotherapy is increasingly used in locally advanced head and neck squamous cell carcinoma. We aimed to compare the incidence of hearing loss between patients treated with intra-arterial high-dose cisplatin chemoradiation with sodium thiosulfate (CRT-IA) and intravenous high-dose cisplatin chemoradiation without sodium thiosulfate (CRT-IV). Patients and Methods We conducted a prospective analysis of hearing thresholds at low and (ultra-) high frequencies obtained before, during, and after treatment in 158 patients. Patients were randomly assigned for either CRT-IA (150 mg/m2, four courses) with sodium thiosulfate cisplatin neutralization or CRT-IV (100 mg/m2, three courses) without rescue. All patients received concomitant radiation therapy (RT; 70 Gy). Results CRT-IA resulted in approximately 10% less hearing loss at frequencies vital for speech perception, compared with CRT-IV (P < .001). In CRT-IA, fewer ears qualified for hearing aids (36% v 49%; P = .03). However, in both treatment arms, the incidence expressed in National Cancer Institute Common Terminology Criteria of Adverse Events (version 3) did not deviate (P > .14). Age, cumulative cisplatin dose, cumulative RT dose, and the considered frequency area determine the degree of hearing loss (P < .001). Cisplatin induced increasing hearing loss of 24% to 60% with increasing frequencies. RT induced hearing loss at speech frequencies of 9% to 12%. Conclusion Depending on the criteria used to assess hearing loss due to treatment, differences in ototoxicity between CRT-IA and CRT-IV were found in favor of CRT-IA. It is desirable to specify hearing loss criteria toward frequencies vital for speech perception, and to refine grading scales to reveal subtle and clinically relevant dissimilarities in ototoxicity between different treatment protocols.
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Affiliation(s)
- Charlotte L Zuur
- Department of Otorhinolaryngology, Academical Medical Centre, Amsterdam, the Netherlands.
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Zuur CL, Simis YJ, Lansdaal PE, Hart AA, Rasch CR, Schornagel JH, Dreschler WA, Balm AJ. Risk Factors of Ototoxicity After Cisplatin-Based Chemo-Irradiation in Patients With Locally Advanced Head-and-Neck Cancer: A Multivariate Analysis. Int J Radiat Oncol Biol Phys 2007; 68:1320-5. [PMID: 17418969 DOI: 10.1016/j.ijrobp.2007.01.042] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2006] [Revised: 01/05/2007] [Accepted: 01/28/2007] [Indexed: 11/28/2022]
Abstract
PURPOSE Cisplatin chemo-irradiation is increasingly used in locally advanced squamous cell carcinoma of the head and neck. The objective of this study is to determine risk factors of ototoxicity due to intra-arterial high-dose cisplatin chemoradiation. METHODS AND MATERIALS A prospective analysis of hearing thresholds at low and (ultra) high frequencies obtained before, during, and after treatment in 146 patients. Treatment consisted of intra-arterial infusion of high-dose cisplatin (150 mg/m(2), four courses) with sodium thiosulfate rescue and concurrent radiation therapy (70 Gy). Patient and chemoradiation variables were studied in a multivariate analysis. RESULTS After treatment, 23% of the ears were under consideration for hearing aids because of therapy. Twenty-two percent of the patients developed an increase in air-bone gap >10 dB during or after therapy. In the multivariate explanatory analysis, cumulative dose of cisplatin and radiation therapy, and young age displayed a causal relationship with increased sensorineural hearing loss during and after therapy (p < 0.001). In the multivariate prediction analysis, pretreatment hearing level of the concerning ear was identified as an independent predictive factor for hearing capability after therapy (p < 0.0001). CONCLUSIONS Both cisplatin and radiation therapy were proven to induce sensorineural hearing loss, in this study with short-term follow-up. Of all patient and treatment variables studied, the patients pretreatment hearing level appeared to be the main predictive factor for hearing capability after high-dose intra-arterial cisplatin chemoradiation.
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Affiliation(s)
- Charlotte L Zuur
- Department of Otorhinolaryngology, Academical Medical Centre, Amsterdam, The Netherlands.
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Rabbani A, Hinerman RW, Schmalfuss IM, Amdur RJ, Morris CG, Peters KR, Robbins KT, Mendenhall WM. Radiotherapy and concomitant intraarterial cisplatin (RADPLAT) for advanced squamous cell carcinomas of the head and neck. Am J Clin Oncol 2007; 30:283-6. [PMID: 17551306 DOI: 10.1097/01.coc.0000258118.38177.74] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE Review of the University of Florida experience in treating advanced squamous cell carcinomas of the head and neck with concurrent intraarterial cisplatin and radiotherapy (RADPLAT). PATIENTS AND METHODS Thirty-five patients with Stage III or IV head and neck squamous cell carcinomas were treated between November 2000 and October 2001 with 3 to 4 cycles of weekly intraarterial cisplatin (150 mg/m2) and a rapid infusion of the neutralizing agent sodium thiosulfate (9 g/m2), followed by a continuous infusion of sodium thiosulfate (12 g/m2), with concomitant radiotherapy (RT). The primary site was treated with 70 Gy in 35 fractions with 6 MV photons, and the low neck received 50 to 70 Gy depending on nodal involvement. Median follow-up for all patients was 4.06 years; median follow-up for living patients was 4.34 years. RESULTS The 4-year outcomes were: local-regional control, 78%; distant metastasis-free survival, 83%; cause-specific survival, 65%; and survival, 57%. The majority of patients with recurrent disease failed at the primary site (73%); the remaining 27% of patients with recurrent disease failed only in distant sites. Nine patients required a neck dissection after chemoradiation because of suspected residual disease; 2 of 9 patients had residual tumor in the neck nodes. Severe osteoradionecrosis occurred in 26% of patients, and 9 of 35 patients (26%) required a permanent gastrostomy. CONCLUSIONS RADPLAT results in excellent local-regional control and survival in patients with advanced squamous cell carcinomas of the head and neck. Outcomes from the University of Florida are comparable to those reported by other institutions. However, in our limited experience, the likelihood of osteoradionecrosis and permanent gastrostomy may be higher than what might be anticipated after RT alone or combined with intravenous chemotherapy.
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Affiliation(s)
- Anna Rabbani
- Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL, USA
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Posch NAS, Mureau MAM, Dumans AG, Hofer SOP. Functional and Aesthetic Outcome and Survival after Double Free Flap Reconstruction in Advanced Head and Neck Cancer Patients. Plast Reconstr Surg 2007; 120:124-129. [PMID: 17572553 DOI: 10.1097/01.prs.0000263656.67904.6a] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Extensive composite defects in the head and neck area may require the use of double free flap reconstructions. These reconstructions are not only surgically challenging but also challenging to patients. A realistic perspective on general outcome for the patient seems important. METHODS From January of 2002 to August of 2003, double free flap reconstructions were used in 12 patients with extensive composite head and neck defects following malignant tumor (n = 7) and osteoradionecrosis (n = 5) resection. Six patients had a standardized interview, physical examination, and clinical photographs. RESULTS All reconstructions were performed using an osteocutaneous fibula flap in combination with an anterolateral thigh flap (n = 8), a radial forearm flap (n = 1), or a lateral thigh flap (n = 1). The total flap survival rate was 96 percent. Mean mandibular bone defects were 10 cm. Mean skin island sizes of osteocutaneous fibula flaps were 67 cm. Mean external skin reconstruction flap sizes were 117 cm. Mean overall survival time was 20 months in patients with malignant tumors. Patients with osteoradionecrosis reconstruction survived free of disease for an average period of 38 months. Three patients (50 percent) were very satisfied, one was neutral, and two were very dissatisfied with their functional and aesthetic results. Objective evaluation of function showed mainly deteriorated speech (83 percent) and oral incontinence (67 percent). Objective evaluation of aesthetics showed mainly color mismatch (67 percent) and flap contracture of external flaps (50 percent). CONCLUSIONS Reconstruction of these major composite through-and-through defects will often result in a modest functional and aesthetic outcome. Because selected patients require these procedures, the authors give information that matches with realistic expectations.
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Affiliation(s)
- Nicole A S Posch
- Rotterdam, The Netherlands From the Departments of Plastic and Reconstructive Surgery and Maxillofacial Surgery, Erasmus Medical Center Rotterdam
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van den Broek GB, Balm AJM, van den Brekel MWM, Hauptmann M, Schornagel JH, Rasch CRN. Relationship between clinical factors and the incidence of toxicity after intra-arterial chemoradiation for head and neck cancer. Radiother Oncol 2006; 81:143-50. [PMID: 17055096 DOI: 10.1016/j.radonc.2006.09.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2006] [Revised: 09/07/2006] [Accepted: 09/12/2006] [Indexed: 11/20/2022]
Abstract
BACKGROUND AND PURPOSE Concomitant chemoradiation is more and more used for advanced head and neck cancer. It improves local control and survival compared to radiotherapy alone, but goes along with serious toxicity. This study was set up to determine the relationship between patient-, tumour- and treatment-related factors and acute/late toxicity after concomitant chemoradiation. PATIENTS AND METHODS One hundred and twenty-five consecutive patients with newly diagnosed inoperable stage III and IV head and neck cancer were enrolled for intra-arterial chemoradiation. There were 28 women (22%) and 97 men (78%) and the mean age was 55 years (range 30-80). One hundred and nine patients had stage IV disease (87%), 16 patients (13%) had stage III disease. Statistical analyses were performed to identify an association between factors and acute/late toxicity. RESULTS There were eight treatment-related deaths (6%). Severe acute toxicity (grade 3-4), mainly mucositis and dysphagia as categorized by the RTOG toxicity criteria, was recorded in 51% of the patients. Leucopenia (grade 3-4) occurred in 39% and aspiration pneumonia in 20% of patients. Tracheotomy was necessary in 15 (12%) patients. Neurological complications during treatment occurred in 3 (2%) patients. Severe late toxicity occurred in 34% of the patients. The most important of these were pneumonia (14%), osteoradionecrosis (9%) and swallowing problems with permanent percutaneous gastrostomy (20%). Statistical analysis did show a significant association between site and severe acute mucositis (p = 0.007), site and osteoradionecrosis (p = 0.014) and age and xerostomia (p = 0.004). CONCLUSIONS Chemoradiation is frequently associated with serious toxicity. Oral cavity tumours and older age are related to acute mucositis/osteoradionecrosis and xerostomia, respectively.
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Affiliation(s)
- Guido B van den Broek
- Department of Head and Neck Oncology and Surgery, Academic Medical Centre, Amsterdam, The Netherlands.
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Gupta R, Thomas AJ, Horowitz M. Intracranial Head and Neck Tumors: Endovascular Considerations, Present and Future. Neurosurgery 2006; 59:S251-60; discussion S3-13. [PMID: 17053610 DOI: 10.1227/01.neu.0000239249.65742.1c] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Abstract
TO REVIEW THE literature on endovascular therapies available to clinicians to aid in the management of head, neck, and intracranial tumors. Hypervascular tumors of the head and neck region, as well as the intracranial region, are associated with large amounts of blood loss intraoperatively. Preoperative embolization of selected hypervascular tumors has been proposed in the literature as a method of reducing blood loss intraoperatively. This technique involves superselective catheterization of the feeding arteries to the tumor bed and then by infusion of embolic particles to saturate the tumor bed in the hopes of inducing necrosis. For less vascular tumors, selective infusion of chemotherapeutic agents has been reported as a method of reducing the systemic toxic effects of these medications. Endovascular therapies for hypervascular and less vascular tumors hold promise, although multicenter randomized controlled trials are required to help identify the patients that will benefit the most.
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Affiliation(s)
- Rishi Gupta
- Department of Neurology, Stroke Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA
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