This study evaluates the safety and efficacy of hypofractionated intensity-modulated radiation therapy (IMRT) following radical hysterectomy.

This phase II, non-randomized multicenter trial included 61 patients with cervical cancer who were eligible for adjuvant RT after radical hysterectomy. Participants received 40 Gy in 16 fractions using IMRT to whole pelvis. The primary endpoint was the incidence of grade 3 or higher acute gastrointestinal, genitourinary, and hematologic toxicities. Secondary endpoints included patient-reported quality of life and disease-free survival (DFS). Acute toxicities were monitored using the National Cancer Institute's Common Terminology Criteria for Adverse Events v4.0.

Among the participants, the incidence of grade 3 or higher acute toxicities was 1.6 % (90 % confidence interval, 0-3.7 %). After a median follow-up of 39.5 months, the 3-year DFS rate was 87.1 %, and no grade ≥ 3 late toxicities were reported during the follow-up period.

Hypofractionated IMRT post-radical hysterectomy demonstrated low severe toxicity rates and effective disease control, suggesting a feasible alternative to conventional fractionation. However, further randomized comparative trials are required to validate the results of this study.

Registered on ClinicalTrials.gov, NCT03239626.

Intensity-modulated radiation therapy (IMRT) uses intensity-modulated photon beams from multiple directions to achieve conformal dose delivery to a target with a complex shape while reducing the dose to organs at risk. We analyzed the trends in IMRT utilization rates across Japanese prefectures from 2015 to 2019 and investigated their relationship with medical resources. Data from the National Database of Health Insurance Claims and the Japanese Society for Radiation Oncology Structure Survey were analyzed. IMRT utilization rates and medical resources (radiation oncologists, medical physicists, radiation technologists, and IMRT-capable linear accelerators) were assessed for all 47 prefectures. A mixed-model analysis was employed to examine the relationship between IMRT utilization rates and medical resources. IMRT utilization increased from 16.4% in 2015 to 22.0% in 2019, with significant regional disparities (range, <10% to >30%). Mixed-model analysis revealed that the number of IMRT-capable linear accelerators (estimate = 0.073, P < 0.01) and radiation oncologists (estimate = 0.032, P = 0.04) was significantly associated with higher IMRT utilization rates. Medical physicists and radiation technologists showed no significant association with IMRT utilization rates. Although the use of IMRT has increased in Japan, substantial regional disparities persist. Increasing the number of IMRT-capable linear accelerators and radiation oncologists may be the most effective strategy to improve equitable access to IMRT in Japan.

The appearance of symptomatic tumor-related vaginal bleeding and pain in advanced incurable cancer patients with pelvic gynecological malignancies remains a therapeutic challenge in oncological treatment. The aim of our analysis was to evaluate the efficacy and safety of palliative hemostatic radiotherapy.

We retrospectively identified patients who had received palliative hemostatic radiotherapy (RT) at our institution between 2011 and 2023 and evaluated acute toxicity, local control, cessation of bleeding, and pain relief.

In total, 40 patients with a median planning target volume of 804 cm3 were treated with a median total dose of 39 Gy in 13 fractions, resulting in 6‑month and 1‑year local control rates of 66.9 and 60.8%, respectively. No higher-grade (>grade III) acute RT-induced toxicity appeared. Complete cessation of bleeding was achieved in 80.0% of all patients after a median of 16 days and pain relief was documented in 60.9% at first follow-up. 37.5% of the women required a blood transfusion and 25% an additional tamponade with local hemostatic agents. Successful stopping of bleeding was significantly less frequent in patients receiving anticoagulation concurrently with radiation and in the case of infield re-irradiation. Patients with a higher total RT dose had cessation of bleeding significantly more often, with a cut-off value of at least EQD2 (α/β = 10) = 36 Gy. The applied RT technique and planning target volume had no significant influence on the occurrence of bleeding cessation.

Palliative hemostatic radiotherapy for locally advanced pelvic gynecological malignancies is safe and effective in achieving high control rates of hemostasis in tumor bleeding and pain relief.

This study aimed to compare oncological outcomes and complication rates between radical hysterectomy (RH) and concurrent chemoradiotherapy (CCRT) in patients with stage IIICr cervical cancer without parametrial invasion, based on differing treatment protocols at two institutions.

A total of 106 patients with biopsy-confirmed cervical cancer and lymph node metastasis detected on pretreatment imaging, but without evidence of parametrial invasion, were enrolled. Of these, 55 patients underwent RH, while 51 patients received CCRT. Oncological outcomes, complication rates, and recurrence patterns were analyzed and compared between the two groups.

At a median follow-up of 62 months (range, 3-220 months), there were no statistically significant differences in disease-free survival or overall survival between the RH and CCRT groups (p = 0.7788 and p = 0.8757, respectively). However, the incidence of overall complications was significantly higher in the RH group compared to the CCRT group (54.5% vs. 19.6%, p < 0.0001). The RH group also demonstrated a significantly greater frequency of major complications (Clavien-Dindo grade III/IV: 23.6% vs. 3.9%, p < 0.0001). Patterns of recurrence differed between the groups: the RH group exhibited a higher rate of distant metastases (56.2% vs. 16.3%), whereas the CCRT group showed a higher incidence of local recurrence (64.3% vs. 25.0%, p = 0.026).

There were no significant differences in disease-free or overall survival between patients treated with RH and those treated with CCRT. However, RH was associated with a significantly higher rate of complications. Given these findings, CCRT may represent a more favorable treatment option for patients with stage IIICr cervical cancer without parametrial invasion.

This study aimed to investigate the impact of bladder volume on dosimetric outcomes of organs at risk (OARs) in postoperative volumetric-modulated arc therapy (VMAT) for patients with cervical cancer.

The study included 71 cervical cancer patients who received radical hysterectomy and postoperative VMAT between January 2020 and January 2023. Patients were divided into 3 groups according to average bladder volume observed in computed tomography simulation positioning images: Group A (<300 mL), Group B (300-500 mL), and Group C (≥500 mL). The study compared dosimetric parameters(V₃₀, V₄₀, V₄₅, and D2cc) for OARs like the bladder, rectum, small intestine, and sigmoid colon, as well as the incidence of radiation cystitis and proctitis among these groups.

The median follow-up of the cohort was 33 months, with a median patient age of 48 years. Group A demonstrated the highest V₄₀ and V₄₅ values for the bladder (p<0.05). Conversely, Group C displayed the highest values for the V₄₀ and V₄₅ of the rectum, as well as the V₄₅ and D2cc of the sigmoid colon (p<0.05). No statistically significant differences were observed in the incidence of acute radiation cystitis and radiation cystitis among the 3 groups. Significant difference was observed in the incidence rates of late radiation cystitis (p<0.05) and radiation proctitis (p<0.05) among the 3 groups. Group A exhibited the highest prevalence of late radiation cystitis, whereas Group C demonstrated the highest prevalence of late radiation proctitis.

Bladder volume significantly affects dosimetry of the bladder, rectum, and sigmoid colon in postoperative VMAT for cervical cancer patients. A recommended bladder volume of 300-500 mL helps reduce radiation-induced cystitis and proctitis.

Patients with node-positive (LN+) uterine or cervical cancer often require postoperative radiation therapy (RT) to the pelvis and para-aortic nodes. A prospective phase 2 study was conducted to evaluate the efficacy of proton beam RT for LN+ uterine or cervical cancer.

Patients with IIIC uterine and cervical cancer post hysterectomy and lymphadenectomy were eligible. Patients received 45 Gy(relative biological effectiveness) in 25 fractions with pencil beam scanning proton therapy (PBS-PT). Primary endpoints included comparing dose-volume histogram and toxicity (National Cancer Institute Common Terminology Criteria for Adverse Events v4.02) between PBS-PT and intensity modulated RT or 3-dimensional conformal RT. Secondary endpoints included progression-free survival, overall survival, patterns of recurrence, and quality of life (QOL using Functional Assessment of Cancer Therapy-Endometrial/Cervix Version 4, FACT-En/Cx V4).

Twenty-one patients completed RT between October 2013 and October 2018. Median follow-up was 60.6 months (range, 11.2-68.8). There were 15 uterine and 6 cervical cancer patients. Four received pelvic and 17 received extended-field RT. Dose-volume histogram comparisons showed significantly less volume treated with PBS-PT compared to 3-dimensional conformal RT and intensity modulated RT for bowel, bone marrow, and kidney (all P < .05) at all dose levels except V45 bladder and bowel. Acute and late grade 3 gastrointestinal toxicity were 14% and 4.7%, respectively. There were no acute or late grade 3 genitourinary toxicities. Acute and late grade 3 hematologic toxicities were 24% and 4.7%, respectively. There was 1 late grade 3 lymphedema. The 2- and 5-year progression-free survival were 81% (95% CI, 56%-92%) and 76% (95% CI, 51%-89%). There were no in-field recurrences. The 2- and 5-year overall survival were 86% (95% CI, 62%-95%) and 80% (95% CI, 55%-92%). QOL increased significantly over time with an average increase of 10.7 points from baseline to 5 years (95% CI, 0.9-20.4, P = .032).

Compared to photon RT, PBS-PT treats significantly less normal tissue volume. PBS-PT appears effective in preventing local-regional recurrence in LN+ patients with minimal acute and late toxicity. QOL significantly improved from baseline to 5 years.

To report toxicity from the multicenter phase III randomized trial of Bladder Adjuvant Radiation Therapy (BART) after radical cystectomy and chemotherapy in high-risk muscle-invasive bladder cancer (MIBC).

Patients with nonmetastatic urothelial MIBC with ≥1 high-risk feature after radical cystectomy- pT3-4, pN1-3, nodal yield <10, positive margin, or ≥cT3 downstaged with neoadjuvant chemotherapy- were randomized 1:1 to observation (Obs) or adjuvant radiation therapy (RT) at 4 centers, stratified by pN stage (N0, N+) and chemotherapy (neoadjuvant, adjuvant, none). Stoma-sparing image guided intensity modulated RT 50.4 Gy in 28# was prescribed to the cystectomy bed and pelvic nodes. Acute toxicity (≤3 months of RT/randomization) and late toxicity were assessed per protocol using Common Terminology Criteria for Adverse Event v5.0. Patients progressing within 3 or 6 months of randomization were excluded from acute or late toxicity analysis, respectively.

The BART trial enrolled 153 patients (Obs = 76, RT = 77). About half (49%) had pN+. Nearly 90% received chemotherapy (70% neoadjuvant; most commonly gemcitabine plus cisplatin). In the RT arm, 63/77 completed RT per protocol with no toxicity-related RT termination. Of the 134 patients analyzable for acute toxicity, no difference was observed in grade 3 (Obs 4.2% vs RT 1.6%, P = .34). Grade 2 effects were higher with RT (17.5% vs 1.1%, P < .001), mainly diarrhea/enteritis or proctitis. Late toxicity was analyzable for 104 patients (Obs = 57, RT = 47) with a median follow-up of 27 months. Grades 3 to 4 toxicity were about 10% (Obs 10.5% vs RT 8.4%, P = .62), and cumulative late grade 2+ toxicity was similar in both groups (17.5% vs 23.3%, P = .27).

In the largest trial of adjuvant RT for high-risk urothelial MIBC, severe acute and late toxicity were low and similar with obervation or radiation therapy. The oncological outcomes are awaited.

Cervical cancer is preventable with screening and vaccination approaches; however, access to these preventative measures is limited both nationally and globally and thus many women will still develop cervical cancer. Novel treatments and practice-changing research have improved cervical cancer outcomes over the past few decades. In this Review, we discuss clinical trials that have refined or redefined the treatment of cervical cancers across the early stage, locally advanced, persistent, recurrent and/or metastatic disease settings. Advances for patients with early stage disease have been achieved through trials evaluating less extensive and fertility-preserving surgeries, different surgical approaches (open versus minimally invasive), and sentinel versus full pelvic lymph node dissection. We also discuss results from trials testing the use of neoadjuvant, induction and adjuvant chemotherapy as well as immune-checkpoint inhibitors in patients with locally advanced disease. Finally, we review the progress made with systemic chemotherapy and novel therapeutics, including anti-angiogenic agents, immune-checkpoint inhibitors and antibody-drug conjugates, in the setting of metastatic and/or recurrent cervical cancer. The advances highlighted in this manuscript have reduced morbidity and improved overall survival for patients with this challenging-to-treat disease, while also inspiring additional research and trials in the field.

Bladder volume variations during radiotherapy can significantly influence dose distribution to both target volumes and surrounding organs-at-risk (OARs). This study aims to assess the dosimetric impact of variable bladder volume on the clinical target volume (CTV) and OARs in cervical cancer patients undergoing MR-guided radiotherapy.

A total of 27 cervical cancer patients were included in this study: 12 received radical radiotherapy, and 15 underwent postoperative radiotherapy. All patients were treated with the Elekta Unity MR-linac system. The dose requirement was 95-100% of the prescribed dose to the PTV(45 Gy/25 sessions/5 weeks). Daily images were acquired at the time of treatment using the MR-linac. For this study, MR images from the first three treatments of each patient were selected to contour the CTV and OAR (bladder, small bowel, rectum, right and left lateral femoral heads), and the treatment plan was recalculated using the Monaco TPS. The dosimetric effects of bladder volume changes on the CTV and OAR were analyzed by SPSS.

Regarding the dosimetric effects on the CTV, in the postoperative radiotherapy group, D98 and D95 of the CTV decreased as the bladder filled. In contrast, for patients undergoing radical radiotherapy, the mean dose of the CTV increased from 5223.55 cGy to 5273.93 cGy as the bladder filled. For the dosimetric effects on the bladder, in the postoperative radiotherapy group, V30 and V20 of the bladder decreased as the bladder filled. In the radical radiotherapy group, the minimum dose of the bladder decreased with increasing bladder volume, but the maximum dose increased from 5347.68 cGy to 5581.63 cGy. For the rectum and small bowel, in the postoperative radiotherapy group, changes in bladder volume did not significantly affect the dose of the small bowel and rectum. However, in the radical radiotherapy group, the minimum and mean doses to the rectum and the D2 of the small bowel decreased with bladder filling.

This study evaluated the dosimetric and volumetric impact of bladder filling on the Clinical Target Volume (CTV) and Organs at Risk (OAR) using daily magnetic resonance (MR) images from the MR-linac. The findings indicate that variations in bladder filling significantly affect dose distribution to both the CTV and OAR.

The objective was to evaluate clinical outcomes and toxicity of patients with cervical cancer treated by radiotherapy with dose escalation in involved lymph nodes based on positron emission tomography/computed tomography (PET/CT) staging.

Retrospective cohort study involving locally advanced cervical neoplasms treated with definitive radiotherapy. Volumetric modulated arc therapy (VMAT), image-guided radiotherapy (IGRT), and registration of PET/CT were employed in all. Involved lymph nodes were given higher doses simultaneously.

Between February 2012 and September 2023, there were 37 patients, with median age of 48 (range 27-91) years. Almost 70% were stages III/IVA. Two-thirds were given retroperitoneal irradiation. The mean delivered doses to primary tumor and to involved lymph nodes were, respectively, 52.5 Gy, and 62.5 Gy. The 10-year rates of overall survival, event-free survival, local-recurrence-free survival, and metastasis-free survival were, respectively, 76%, 50%, 91%, and 82%. There were 13 and 2 cases of gastrointestinal toxicity grades II and III, respectively. Grades II and III of genitourinary toxicity were seen respectively in 7 and 3 patients. On univariate analysis, age was related to local recurrence-free survival (LRFS); standard uptake values (SUV) was related to event-free survival (EFS); lymph node dose was related to overall survival (OS), and EFS; primary tumor dose was directly related to EFS, albeit inversely to the likelihood of grade > II gastrointestinal toxicity. Retroperitoneal irradiation improved LRFS, and rates of grade > II gastrointestinal toxicity. On multivariate analysis, SUV remained an independent predictor of EFS; lymph node dose was an independent predictor of OS, and age was an independent predictor of lymph node recurrence.

Dose escalation radiotherapy (RT) based on PET/CT for cervical cancer may be feasible and safe. Further robust study results are needed.

Radiotherapy, administered with or without chemotherapy is the gold standard treatment for cervical cancer with both curative and palliative intent. However, the treatments often result in adverse events, mainly chronic pelvic pain and bowel morbidity, which can negatively impact quality of life.

To systematically appraise peer reviewed evidence regarding chronic pelvic pain and bowel morbidity and their impact on quality-of-life of cervical cancer patients treated with radiotherapy with or without chemoradiation therapy.

A systematic review of original peer-reviewed research evidence.

A systematic search conducted between April and May 2021, and updated in September 2024, using PubMed, Hinari, CINAHL and Google Scholar, for peer reviewed papers published between 2008 and 2019. Data were extracted using a structured checklist designed to capture key elements about the methods and findings of the research.

There were 245 articles retrieved with 29 meeting the inclusion criteria. 11 studies were conducted in Europe, eight in Asia, one in North America, three in Africa, while six were multinational/multicontinental. 13 of the papers were longitudinal, 10 cross-sectional, three literature reviews, one open randomised controlled trial, and two retrospective studies of prospectively collected data. Studies reported disruptions in nearly all domains of quality-of-life, including global, physical, emotional/psychological, financial, sexual, social, role functioning as a result of being treated with radiotherapy or radio-chemotherapy.

Chronic pelvic pain and bowel morbidity are common adverse events experienced by cervical cancer patients receiving, or who have received, pelvic radiotherapy or radio-chemotherapy. Symptoms occur to varying degrees and exert a negative toll on the quality-of-life of women. Clinicians should be more aware and prioritise thorough assessment and management of symptoms before, during and after treatment. There is limited population-based and longitudinal research about the topic, and on chronic pelvic pain in general, which limits generalisability. Longitudinal studies with more extended periods of follow-up are needed.

This study aimed to determine the feasibility of increasing soluble fibre intake via dietary counselling to improve gastrointestinal toxicity and quality of life in patients with gynaecological cancers undergoing pelvic radiotherapy without adverse consequences on radiation treatment (RT) delivery accuracy.

A single-arm, single-centre intervention feasibility trial included patients with gynaecological cancers undergoing pelvic RT ± chemotherapy at a tertiary hospital. Participants were provided weekly dietary counselling over the duration of their RT (5-6 weeks) to increase soluble fibre intake incrementally each week. Stakeholder surveys were also completed.

In total, 9 of 14 eligible patients participated (55 years old [SD 13.2], diagnosis: cervical [n = 3], endometrial/uterine [n = 5] and vaginal [n = 1]), with the majority categorised as low fibre consumers at baseline (n = 6). On average, soluble fibre intake increased by 150% throughout treatment. There were no adverse events or major adjustments required for RT delivery. There were improving trends in the functional subset identified. Results may be confounded by the sample size resulting from limited eligibility (n = 14) and a high attrition rate (n = 4).

Most participants successfully increased their soluble fibre intake throughout treatment, without significant adverse events noted for RT delivery accuracy. These results provide preliminary data to calculate the sample size required to produce meaningful effect sizes. However, this study highlighted challenges in participant recruitment and retention, with limited organisational support and perceived compatibility.

There is evidence that proper radiotherapy trial quality assurance (RTTQA) translates into improved outcomes for patients. However, the practice of RTTQA is heterogeneous and implemented in a diverse manner across trials. In this paper, we review the RTTQA report for randomised trials (RCT) conducted in India and present our experience with RTTQA for various clinical trials and highlight the key achievements and challenges.

Search was performed using the keywords and the variations thereof for "radiotherapy" and author affiliations from India, its states and major metropolitan cities. Pubmed search filters were used to restrict results to RCT published in the past 5 years (2019-2024). Reporting of RTTQA procedures from publications and protocols was documented along with the protocol-specified dosimetric goals. We also evaluated a few clinical trials performed in the Department of Radiation Oncology at Tata Medical Center. The different RTTQA procedures and results for four representative clinical trials have been described.

A formal RTTQA process was reported by only one out of 24 randomised controlled trials and formal dosimetric goals were pre-specified by 9 of 13 trials where IMRT was used as treatment. RTTQA requirements were tailored for each clinical trial at Tata Medical Center. For the HYPORT trial, the RTTQA process focused on ensuring the matchline doses were homogenous. HYPORT B trial commissioned the use of a simultaneous integrated boost technique which emphasised conformal avoidance of dose spillage to contralateral breast and lung. HYPORT Adjuvant and PROPARA trials are multicentre clinical trials. While HYPORT Adjuvant focussed on ensuring that the dose delivery met the predefined constraints, segmentation of the target volume was important for the PROPARA trial.

We demonstrate different RTTQA procedures required for representative clinical trials and highlight key challenges encountered.

Adaptive radiotherapy (ART) provides greater benefits than intensity-modulated radiotherapy (IMRT) regarding dosimetric outcomes in patients with cervical cancer. To investigate the clinical benefits of ART, we have collected data from 115 cervical cancer patients who underwent radical radiotherapy at our institution. Fifty-nine patients received a single course of IMRT. Fifty-six patients underwent offline ART, defined as the reduction of the gross tumor volume (GTV) by at least 30% after 30 Gy of radiotherapy, followed by a modified treatment plan for the second-stage. After treatment, 53 patients of ART group achieved a partial response (PR) or completement response (CR), resulting in an objective response rate (ORR) of 94.6% for the ART group, compared to 93.2% for the IMRT group. Patients in both groups exhibited no significant differences in acute toxicities. However, the incidence of chronic constipation was significantly higher in the IMRT group compared to the ART group (p = 0.021). With a median follow-up time of 27 months, the ART group experienced a higher mortality (10/56) than the IMRT group (6/59). However, the difference between the two groups was not statistically significant. In summary, ART may be advantageous in reducing the incidence of chronic constipation among patients with locally advanced cervical cancer, and both clinical prognosis and near-term survival are satisfactory.

To compare ileal conduit (IC) and other organ at risk (OAR) dosimetry between treatment techniques in a prospective cohort of patients planned for adjuvant radiotherapy (RT) after radical cystectomy and IC reconstruction.

Computed tomography (CT datasets of twenty patients who underwent adjuvant RT were obtained and used prospectively for delineation of target volumes (primary and nodal) and OARs, including IC, uretero-ileal anastomosis and ileal stoma using a specified protocol for simulation including a delayed CT to identify IC. Three RT plans were generated for each patient for a dose of 54 gray (Gy) in 27 fractions (PTV V95% >95%): 3-dimensional conformal radiotherapy (3DCRT) with (3DCRT_S) and without (3DCRT_N) stoma shielding, and volumetric modulated arc therapy (VMAT), with OAR constraints specified for VMAT plans (IC: Dmax<54Gy, V50Gy < 20 cc). Constraints were given for other pelvic OARs (bowel, rectum, femur heads) as per published literature. Plans were evaluated for target coverage as well as OAR doses; in particular, IC and ileal stoma). ANOVA test was used to compare medians of achieved doses, and a p-value <0.05 was statistically significant.

The median IC volume was 63.34 (55.29-82.93) cc. The cranial end of IC was at L5 or L4 vertebral level in 95% of patients and caudal level at S2 or S3 in 80% of patients. In contrast, the ileal stoma spanned from L4 or L5 vertebral level cranially (100%) to L5 level caudally (80%). PTV V95% was similar for 3DCRT_N and VMAT plans while it was significantly lower for 3DCRT_S in areas of ileal stoma shielding (99.95% vs 99.01% vs 96.29%, p < 0.01). Median IC V50Gy was comparable in 3DCRT_N (38.81 cc) and 3DCRT_S (35.62 cc) while it was significantly lower in the VMAT plan (17.05 cc, p < 0.01). IC Dmax did not differ significantly between the three plans. On the other hand, when 3DCRT_N, 3DCRT_S, and VMAT plans were compared for ileal stoma doses, Dmean was comparable (11.93 Gy vs 7.41 Gy vs 9.54 Gy, p = 0.06) while Dmax was significantly higher for 3DCRT_N plan and least for VMAT plan (35.32 Gy vs 27.57 Gy vs 24.22 Gy, p < 0.01). VMAT plans fared significantly better than both 3DCRT plans for uretero-ileal anastomosis, bowel, and rectal dosimetry.

Ileal stoma shielding in 3DCRT compromises PTV coverage but does not spare IC effectively. Sparing IC with VMAT is feasible without compromising PTV coverage. Dosimetric gains with VMAT are expected to benefit patients needing higher pelvic RT doses and nodal RT by reducing the risk of anastomotic and mucosal complications. Clinical benefits should be evaluated in a prospective protocol.

The aim was to determine which immobilisation device improved inter-fraction reproducibly of pelvic tilt and required the least pre-treatment setup and planning interventions.

Sixteen patients were retrospectively reviewed, eight immobilised using the BodyFIX system (BodyFIX®, Elekta, Stockholm, Sweden) and eight using the Butterfly Board (BB) (Bionix Radiation Therapy, Toledo, OH, USA). The daily pre-treatment images were reviewed to assess setup variations between each patient and groups for pelvic tilt, pubic symphysis, sacral promontory and the fifth lumbar spine (L5).

Compared with the planning CT, pelvic tilt for most patients was within ±2° using the BodyFIX and ± 4° for the BB. The Butterfly Board had a slightly higher variance both for patient-to-patient (standard deviation of the systematic error) and day-to-day error (standard deviation of the random error). Variance in position between individual patients and the two stabilisation devices were minimal in the anterior-posterior (AP) and superior-inferior (SI) direction for the pubic symphysis, sacral promontory and L5 spine. Re-imaged fractions due to pelvic tilt reduced by about half when BodyFIX was used (39.1% BB, 19.4% BodyFIX). One patient treated with the BB required a re-scan for pelvic tilt. Three patients required a re-scan for body contour variations (two using BodyFIX and one with the BB).

BodyFIX resulted in a more accurate inter-fraction setup and efficient treatment and is used as the standard stabilisation for gynaecological patients at our centre. It reduced the pelvic tilt variance and reduced the need for re-imaging pre-treatment by half.

The field of gynaecologic oncology has evolved rapidly in recent years, largely driven by advances in both radiotherapy and systemic therapies. These innovations have reshaped the management of key gynaecologic cancers, including cervical, endometrial, vaginal, and vulvar cancers, leading to more personalized and effective treatment approaches. This review explores pivotal clinical trials conducted between 2023 and 2024 that have potentially modified current practices. Through an extensive analysis of randomized controlled trials and meta-analyses, we examine the evolving role of radiotherapy, the integration and sequencing of immunotherapy, and the refinement of neoadjuvant and adjuvant treatments based on molecular classifications. The combination of immunotherapy with chemoradiotherapy has shown promising outcomes, particularly in patients with locally advanced cervical cancer. For endometrial cancer, molecular profiling has enabled a more precise classification of tumour subtypes, leading to better-targeted adjuvant therapies that reduce unnecessary interventions and increase treatment efficacy. In parallel, radiotherapy has advanced with the increasing use of modern techniques such as intensity-modulated radiotherapy and more recently the developments of adaptive treatments in order to minimize exposure to healthy tissue, thereby reducing toxicity and enhancing patient quality of life. Integration of image-guided brachytherapy and expansion of capabilities with newer generation of brachytherapy applicators have also increased possibilities to achieve efficient local treatments, including in very advanced cases. However, despite progress in common gynaecologic cancers, the management of rare cancers such as vulvar and vaginal cancers continues to face challenges due to limited clinical research and treatment data. This review highlights the transformative potential of these innovations and emphasizes the need for continued research and personalized treatment strategies to optimize patient outcomes in gynaecologic oncology.

Background/Objectives. Adult medulloblastoma (AMB) patients should receive postoperative craniospinal irradiation (CSI) as a standard treatment. Volumetric intensity-modulated arc therapy (VMAT) is a promising method for CSI. This report summarizes the repositioning and dosimetric data outcomes for six AMB patients. Methods. Complete CSI and posterior cranial fossa irradiation, or tumor bed boost irradiation with Linac-based VMAT, was performed and evaluated. Patients were immobilized in the supine position with two thermoplastic masks (head-neck and abdomen). To ensure inter-fraction reproducibility during radiotherapy (RT), a single cone-beam CT (CBCT) scan for each isocenter and real-time surface-guided RT using AlignRT® were performed daily before and during the RT session. Match values of all three translational axes (x = lateral, y = longitudinal, z = vertical) were recorded. Results. From August 2022 to September 2023, six AMB patients were treated with CSI: three women and three men with a median age of 32 (22-42). All cases were classical MB, four were low risk, and two were defined as high risk due to the metastatic disease. All patients underwent surgery; two received a gross total resection. Low-risk patients received 36 Gy for CSI and a 54 Gy boost, while high-risk patients received 39 Gy for CSI. No significant toxicities greater than G2 were observed during RT, and only two cases reported decreased platelet counts. The dose to the organs at risk was low and acceptable. The mean dose to the heart, lungs, eyes, stomach, and thyroid were 4.4 Gy, 8.5 Gy, 12 Gy, 8.7 Gy, and 11 Gy, respectively. In terms of repositioning data, 124 CBCT scans were analyzed. Inter-fraction CBCT mean values for the study population in all translational directions were inferior to 2 mm in more than 90% of cases. Conclusions. VMAT is a convenient and effective treatment for AMB. Positioning and immobilization with masks (head and neck plus abdomen) reduce inter-fraction motion.

The standard treatment of locally advanced cervical carcinoma is radical chemoradiation followed by brachytherapy which has improved survival. Hence, a major concern is our attempt to reduce the incidence of acute and late toxicities. IMRT has been shown to reduce toxicities. In this study, we have compared 3DCRT with IG-IMRT using patient-specific margins to evaluate tumor control as well as OAR-related toxicities.

This was a single institution prospective phase III randomised control study including patients of squamous cell carcinoma of cervix (stage II-IIIB, FIGO 2009) without pelvic lymph node involvement. All patients were simulated using intermediate bladder filling protocol and those in the IG-IMRT arm, underwent additional scans with full and empty bladder to assess the range of internal motion and generate individualised ITV margin. EBRT dose of 46Gy/23#/4.5 weeks was delivered with weekly concurrent cisplatin followed by brachytherapy. All toxicities during EBRT and till 3 months post brachytherapy were considered acute toxicity. Post-treatment, patients were followed up every 2 months for first 2 years and then once every 6 months. Disease-related outcomes were assessed with clinical examination and symptom-directed imaging.

Two hundred patients were screened for inclusion and of them, 89 patients in 3DCRT and 84 patients in IG-IMRT arms were considered for final analysis. The baseline characteristics were comparable in both arms, majority of patients in both arms having stage II disease. For OARs, all dosimetric parameters were significantly better in the IG-IMRT arm. Acute radiation induced toxicities (dermatitis, genito-urinary and gastrointestinal toxicities) were significantly less in the IG-IMRT arm. The local, pelvic, and distant control were comparable in both arms.

Based on our experience, the use of IG-IMRT with patient-specific ITV margins results in reduction in acute OAR toxicities in patients without compromising on tumor control.

The information on the practice of radiotherapy, including intensity-modulated radiotherapy (IMRT) use for rectal cancer in India, is lacking. This national survey was planned to understand the current status of knowledge, attitudes, and practice among radiation oncologists, specifically concerning the practice of IMRT for rectal cancers.

A national survey was sent to radiation oncologists through e-mail or a WhatsApp message, where feasible, with a request letter containing the link to the survey questionnaire. The survey questionnaire was adapted from the UK IMRT survey with permission from the authors. It explored rectal cancer management, IMRT use, reasons for nonadoption, total neoadjuvant therapy (TNT), dose fractionation schedules and radiotherapy processes like radiotherapy simulation, target volume/organ at risk definition, and treatment planning, evaluation, and verification. Descriptive statistics is used to present the results.

Over 300 radiation oncologists were approached, and 182 (60.6%) of the 153 institutes responded. Around 88% (160 of 182) indicated using IMRT or volumetric modulated arc therapy (VMAT) to treat rectal cancer, of whom 32% used exclusively IMRT/VMAT in all their patients. The reasons for not adopting IMRT were affordability/lack of insurance, resource constraints, and lack of guidelines. Long-course chemoradiation (capecitabine-based) followed by surgery was the most common neoadjuvant approach, with short course and TNT in less than a third of patients. Daily verification feasibility was reported by 60%. Seventy-three percent emphasized the need for a national IMRT guidance document.

This national survey from India indicates a scope of routine implementation of IMRT in rectal cancer, highlighting the urgent need for a national IMRT guidance document, which could significantly enhance the quality of care for patients with rectal cancer in India.

Radiotherapy is an effective treatment method for cervical cancer and is typically administered as external beam radiotherapy followed by intracavitary brachytherapy. In Japan, center shielding is used in external beam radiotherapy to shorten treatment time and reduce the doses delivered to the rectum or bladder. However, it has several challenges, such as uncertainties in calculating the cumulative dose. Recently, external beam radiotherapy has been increasingly performed with intensity-modulated radiotherapy, which reduces doses to the rectum or bladder without center shielding. In highly conformal radiotherapy, uncertainties in treatment delivery, such as inter-fractional anatomical structure movements, affect treatment outcomes; therefore, image-guided radiotherapy is essential for appropriate and safe performance. Regarding intracavitary brachytherapy, the use of magnetic resonance imaging-based image-guided adaptive brachytherapy is becoming increasingly widespread because it allows dose escalation to the tumor and accurately evaluates the dose delivered to the surrounding normal organs. According to current evidence, a minimal dose of D90% of the high-risk clinical target volume is significantly relevant to local control. Further improvements in target coverage have been achieved with combined interstitial and intracavity brachytherapy for massive tumors with extensive parametrical involvement. Introducing artificial intelligence will enable faster and more accurate generation of brachytherapy plans. Charged-particle therapies have biological and dosimetric advantages, and current evidence has proven their effectiveness and safety in cervical cancer treatment. Recently, radiotherapy-related technologies have advanced dramatically. This review provides an overview of technological innovations and future perspectives in radiotherapy for cervical cancer.

Bevacizumab serves as an effective treatment in cervical cancer patients with metastatic, recurrent, or advanced disease. However, gastrointestinal (GI)/genitourinary (GU) toxicities have been observed after bevacizumab treatment. Radiotherapy (RT) is the mainstay of treatment of cervical cancer.

To investigate the risk of GI/GU toxicities with bevacizumab plus RT compared with RT alone in cervical cancer patients.

In this meta-analysis, PubMed, Embase, Web of Science, and Cochrane databases were searched from inception to September 25, 2022.

Cohort studies evaluating the association between bevacizumab and GI/GU fistula or perforation in irradiated metastatic, recurrent, or advanced cervical cancer patients.

Results are expressed as odds ratios (OR) with 95% confidence intervals (CI). The inconsistency test (I2) was used to assess heterogeneity. Egger's regression test with a two-tailed P value was used to evaluate publication bias.

Four cohort studies met the inclusion criteria with a total of 597 women included. There was a significant association between GI fistula/perforation and GU fistula/perforation in irradiated cervical cancer patients receiving bevacizumab (OR 4.03 [95% CI: 1.76-9.20] and OR 4.71 [95% CI: 1.51-14.70], respectively).

The bevacizumab-containing regimen was associated with an increased risk of GI or GU toxicities in cervical cancer individuals undergoing pelvic RT. These results suggest the bevacizumab-associated benefits and risk should be better weighted to reach an optimal treatment strategy. Further investigation on optimal dosage and timing of bevacizumab and RT is vital to minimize the adverse events and maximize the benefits.

Radiotherapy plus concurrent chemotherapy is a standard method for treating locally advanced cervical cancer (LACC). Immune checkpoint inhibitors (ICIs) are widely applied in the treatment of recurrent cervical cancer, metastatic cervical cancer or LACC. The efficacy and safety of radiotherapy plus immunotherapy for LACC require further investigation. The objective of this review and meta-analysis was to analyze the efficacy and safety of concurrent chemoradiotherapy (CCRT) combined with ICIs for treating LACC on the basis of the results of randomized controlled trials (RCTs).

We comprehensively searched electronic databases to identify RCTs that focused on CCRT plus ICIs for LACC treatment. The outcomes included the objective response rate (ORR) and progression-free survival (PFS), overall survival (OS) and adverse events (AEs). A standard method for systematic review and meta-analysis was used. Review Manager 5.4 was used for data combination and analyses.

Three RCTs involving 1882 participants with LACC were identified and included in the systematic review and meta-analysis. CCRT plus ICIs improved the rates of PFS (hazard ratio [HR]: 0.76, 95% confidence interval [CI]: CI: 0.64, 0.91, P = 0.002) and OS (HR: 0.7695% CI (95% CI 0.58-0.99, P = 0.04) in patients with LACC. Compared with the control group, the CCRT plus immunotherapy group had an increased ORR (OR: 1.37, 95% CI: 1.02,1.85, P=0.04). The two methods had similar rates (HR=1.99, 95% CI: 0.99, 1.43; P=0.07) of treatment-related grade 3 or higher AEs. The CCRT plus immunotherapy group had a higher rate than did the control group (HR: 2.68, 95% CI: 1.38, 5.21; P=0.004) in terms of any grade immunotherapy-related AEs.

CCRT plus ICIs is efficacious and safe for the management of LACC. The addition of ICIs to CCRT improved the rates of PFS and OS in patients with LACC. The adverse effects of immunotherapy-related AEs should be strictly examined and managed in a timely manner.

Hypofractionated radiotherapy (RT) has become a trend in the modern era, as advances in RT techniques, including intensity-modulated RT and image-guided RT, enable the precise and safe delivery of high-dose radiation. Hypofractionated RT offers convenience and can reduce the financial burden on patients by decreasing the number of fractions. Furthermore, hypofractionated RT is potentially more beneficial for tumors with a low α/β ratio compared with conventional fractionation RT. Therefore, hypofractionated RT has been investigated for various primary cancers and has gained status as a standard treatment recommended in the guidelines. In genitourinary (GU) cancer, especially prostate cancer, the efficacy, and safety of various hypofractionated dose schemes have been evaluated in numerous prospective clinical studies, establishing the standard hypofractionated RT regimen. Hypofractionated RT has also been explored for gynecological (GY) cancer, yielding relevant evidence in recent years. In this review, we aimed to summarize the representative evidence and current trends in clinical studies on hypofractionated RT for GU and GY cancers addressing several key questions. In addition, the objective is to offer suggestions for the available dose regimens for hypofractionated RT by reviewing protocols from previous clinical studies.

Multi-modal therapies for gynecological cancers management may determine a wide range of side effects which depend on therapy-related factors and patient characteristics and comorbidities. Curative or adjuvant pelvic radiotherapy is linked with acute and late toxicity due to irradiation of organs at risk, as small and large bowel, rectum, bladder, pelvic bone, vagina and bone marrow. Successful toxicity management varies with its severity, Radiation Centre practice and experience and skills of radiation oncologists. This position paper was designed by the Italian Association of Radiation and Clinical Oncology Gynecology Study Group to provide radiation oncologists with evidence-based strategies to prevent and manage acute and late toxicities and follow-up recommendations for gynecological cancer patients submitted radiotherapy. Six workgroups of radiation oncologists with over 5 years of experience in gynecologic cancers were setup to investigate radiotherapy-related toxicities. For each topic, PubMed database was searched for relevant English language papers from January 2005 to December 2022. Titles and abstracts of results were checked to verify suitability for the document. Reference lists of selected studies and review papers were added if pertinent. Data on incidence, etiopathogenesis, prevention, treatment and follow-up of acute and late side effects for each organ at risk are presented and discussed.

Image guidance is recommended for patients undergoing intensity-modulated radiation therapy (IMRT) for cervical cancer. In this study, we evaluated the feasibility of a weekly image guidance pattern and analyzed the long-term outcomes in a large cohort of patients.

The study enrolled patients with Stage IB-IVA cervical cancer who received definitive radiotherapy or concurrent chemoradiotherapy. IMRT was delivered at a dose of 50.4 Gy in 28 fractions, with weekly cone-beam computed tomography (CBCT). Physicians advised patients on rectum and bladder preparation to help them prepare on nonimaging guidance days. When significant tumor regression was observed, a second computed tomography simulation and replanning were performed.

The median follow-up periods were 63.4 months. The incidence rates of loco-regional and distant failure were 9.9% and 13.6%. The 5-year overall survival (OS), disease-free survival (DFS), loco-regional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 80.1%, 72.9%, 78.3%, and 74.8%, respectively. For patients with different stages, the 5-year OS, DFS, LRFS, and DMFS rates were statistically significant. For patients with and without positive regional lymph nodes, the 5-year OS, DFS, LRFS, and DMFS rates were 64.5% and 86.0%, 56.8% and 78.8%, 62.7% and 84.3%, and 58.8% and 81.0%, respectively. Multivariate analysis showed that age, histology, tumor size, cancer stage, pretreatment squamous cell carcinoma antigen level, and para-aortic metastatic lymph nodes were independent prognostic factors of OS. Fifty-six (4.0%) patients experienced late Grade 3/4 chronic toxicities.

IMRT with weekly CBCT is an acceptable image guidance strategy in countries with limited medical resources.

To report the results of a multicenter cohort of preoperative brachytherapy (PBT) for treatment of early-stage cervical cancer (ESCC).

A retrospective analysis was conducted among five French comprehensive cancer centers on behalf of the SFRO Brachytherapy Group to examine the outcome of patients with ESCC who received PBT between 2001 and 2019 because of adverse prognostic factors (tumor size >2 cm, presence of lymphovascular invasion, adenocarcinoma).Brachytherapy was followed 4-8 weeks later by surgery. Local relapse free, distant metastasis-free survival, disease-free, and overall survival and adverse effects were examined. Uni- and multivariate analyses were conducted looking for oncological prognostic factors.

A total of 451 patients were identified, with a mean tumor size of 24.7 mm. Adenocarcinoma accounted for 43.5% of cases, and lympho-vascular space invasion (LVSI) was present in 15.7%. A complete histological response was observed in 69.6%. With a mean follow-up of 75.4 months, DFS, LRFS, and OS rates at five years were 88% [95% CI (84-91), 98% [95% CI (96-99), and 92% [95% CI (87-95)], respectively. At the last follow-up, 8.2% of patients had died, including 31 (6.8%) from cervical cancer. Severe side effects range from 1.1% to 2%. At multivariate analysis, adenocarcinoma histological type, tumor size ≥2 cm, and the presence of residual tumors were prognosticators for DFS and DMFS.

PBT shows excellent oncological outcomes in this cohort of patients with adverse histoprognostic factors. Favorable survival rates and low complications rates were observed, supporting this strategy in the management of ESCC.

The combination of ferroptosis and innovative tumor therapy methods offers another promising answer to the problem of tumors. In order to generate effective ferroptosis in tumor cells, iron-based nanomaterials are commonly utilized to introduce foreign iron as a trigger for ferroptosis. However, this usually necessitates the injection of larger doses of iron into the body. These exogenous iron increases are likely to create concealed concerns for symptoms such as liver damage and allergy. Herein, an iron-free radiosensitizer is introduced, oxygen-vacancy-rich MnO2 nanoflowers (ovs-MnO2), that promotes ferroptosis and modifies the tumor microenvironment to assist radiotherapy. ovs-MnO2 with enriched oxygen vacancies on the surface induces the release of intracellular free iron (Fe2+), which functions as an activator of Fenton reaction and enhances the accumulation of intracellular reactive oxygen species. On the other hand, Fe2+ also triggers the ferroptosis and promotes the accumulation of lipid peroxides. Subsequently, the depletion of glutathione and accumulation of lipid peroxidation in tumor cells leads to the inactivation of glutathione peroxidase 4 (GPX4) and ferroptosis, thereby enhancing the therapeutic efficacy of radiotherapy. The nanoplatform provides a novel strategy for generating novel nanomedicines for ferroptosis-assisted radiotherapy.

Locally advanced carcinoma cervix (LACC) is a heterogeneous disease with variable combinations of primary tumour extensions with or without nodal involvement. Metabolic information from 18 fluro-deoxyglucose positron emission tomography combined with contrast-enhanced computerized tomography (FDG PET-CT) may potentially augment treatment decision-making for LACC. This study ascertained FDG-PET CT influence on chemoradiation therapy (CTRT) decisions in LACC. We report oncologic and patient-reported outcome measures (PROMs).

FDG PET-CT scans were reviewed independently by two nuclear medicine specialists and two radiation oncologists. Pelvic CTRT plan digressions were documented and therapy was adapted accordingly. Pelvis radiation (50 Gy/25#/5 weeks) using tomotherapy with weekly cisplatin was used in node-negative disease. Dose-escalated simultaneous integrated boost (SIB) 60 Gy/25#/5 weeks was delivered to involved pelvic nodes. All received brachytherapy. Post-treatment PET-CT scans were at 6 months. Functional assessment of cancer therapy scores were calculated at baseline, treatment completion, 3 months, 1 year and 3 years.

Between November 2015 and January 2018, 85 patients were screened, and 77 consented. Extrapelvic disease was seen in 12 (16%) patients (9 para-aortic nodes, 2 distant metastases and 1 synchronous carcinoma breast); 60 patients were included in the final analysis. Decision changes were seen in 10/77 (13%) screened, 8/60 (13%) included and 32 (53.3%) received SIB. Post-treatment, 27 (45%) had grade 2 GI/GU/GYN toxicity, one (2%) had grade 3 GI and five (8.3%) had grade 3 neutropenia. At median follow-up of 54.2 months (95% CI 52.8-58.3), 5-year local failure, pelvic nodal and para-aortic nodal-free survival were 86.8% (95% CI 78.0-96.6), 85.2% (95% CI 76.1-95.3) and 85.2% (95% CI 76.2-95.4). Functional assessment of cancer therapy trial outcome index (FACT TOI) improved by 10.43 at 3 months with no further decline. Grade 3 toxicity was noted for abdominal pain in one (1.7%), cystitis in four (6.7%) and lymphoedema in one (1.7%) at 5 years.

PET-CT resulted in major decision changes in 13%. PET-adapted CTRT was associated with acceptable toxicity, encouraging long-term survival and improvement in PROMS.

Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer. We investigated how additional bone marrow sparing (BMS) affects the clinical outcomes.

We queried MEDLINE, Embase, Web of Science Core Collection, Google Scholar, Sinomed, CNKI, and Wanfang databases for articles published in English or Chinese between 2010/01/01 and 2023/10/31. Full-text manuscripts of prospective, randomised trials on BMS in cervical cancer patients treated with definitive or postoperative CRT were included. Risk of bias (RoB) was assessed using Cochrane Collaboration's RoB tool. Random-effects models were used for the meta-analysis.

A total of 17 trials encompassing 1297 patients were included. The majority were single-centre trials (n = 1268) performed in China (n = 1128). Most trials used CT-based anatomical BMS (n = 1076). There was a comparable representation of trials in the definitive (n = 655) and postoperative (n = 582) settings, and the remaining trials included both.Twelve studies reported data on G ≥ 3 (n = 782) and G ≥ 2 (n = 754) haematologic adverse events. Both G ≥ 3 (OR 0.39; 95 % CI 0.28-0.55; p < 0.001) and G ≥ 2 (OR 0.29; 95 % CI 0.18-0.46; p < 0.001) toxicity were significantly lowered, favouring BMS. Seven studies (n = 635) reported data on chemotherapy interruptions, defined as receiving less than five cycles of cisplatin, which were significantly less frequent in patients treated with BMS (OR 0.44; 95 % CI 0.24-0.81; p = 0.016). There was no evidence of increased gastrointestinal or genitourinary toxicity.There were no signs of significant heterogeneity. Four studies were assessed as high RoB; sensitivity analyses excluding these provided comparable results for main outcomes. The main limitations include heterogeneity in BMS methodology between studies, low representation of populations most affected by cervical cancer, and insufficient data to assess survival outcomes.

The addition of BMS to definitive CRT in cervical cancer patients decreases hematologic toxicity and the frequency of interruptions in concurrent chemotherapy. However, data are insufficient to verify the impact on survival and disease control.

To investigate differences in standard clinico-radiological evaluation versus Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for reporting survival outcomes in patients with locally advanced cervical cancer treated with chemoradiation and brachytherapy.

Between November 2017 and March 2020, patients recruited in cervical cancer trials were identified. MRI at diagnosis and at least one follow-up imaging was mandatory. Disease-free survival and progression-free survival were determined using standard evaluation (clinical examination and symptom-directed imaging) and RECIST 1.1. Agreement between criteria was estimated using κ value. Sensitivity analysis was done to test the sensitivity, specificity, and accuracy of RECIST 1.1 in detecting response to treatment.

Sixty-nine eligible patients had at least one target lesion. Thirty-three patients (47.8%) had pathological lymph nodes. Of these 33 patients, RECIST 1.1 classified only 18% (6/33) as 'target nodal lesions' and the remaining nodes as 'non-target'. There were 6 (8.7%) and 8 (11.6%) patients with disease events using RECIST 1.1 and standard evaluation, respectively. The disease-free survival at 12, 18, and 24 months using RECIST 1.1 was 94.2%, 91.2%, 91.2%, and with standard evaluation was 94.2%, 89.7%, and 88.2%, respectively (p=0.58). Whereas, progression-free survival at 12, 18, and 24 months using RECIST 1.1 and standard evaluation were same (94.2%, 91.2%, and 91.2%, respectively). The κ value was 0.84, showing strong agreement in assessing disease-free survival, although an absolute difference of 3% between endpoint assessment methodologies. RECIST 1.1 had a sensitivity of 75% (95% CI 34.91% to 96.81%), specificity of 100% (95% CI 94.13% to 100%), and accuracy of 97.1% (95% CI 89.92% to 99.65%).

The study showed 1.5% and 3% difference in disease-free survival at 18 and 24 months and no difference in progression-free survival between RECIST 1.1 and standard evaluation in a patient cohort with low event rate.

Insurance barriers to cancer care can cause significant patient and clinician burden.

To investigate the association of insurance denial with changes in technique, dose, and time to delivery of radiation oncology treatment.

In this single-institution cohort analysis, data were collected from patients with payer-denied authorization for radiation therapy (RT) from November 1, 2021, to December 8, 2022. Data were analyzed from December 15, 2022, to December 31, 2023.

Insurance denial for RT.

Association of these denials with changes in RT technique, dose, and time to treatment delivery was assessed using χ2 tests.

A total of 206 cases (118 women [57.3%]; median age, 58 [range, 26-91] years) were identified. Most insurers (199 [96.6%]) were commercial payers, while 7 (3.4%) were Medicare or Medicare Advantage. One hundred sixty-one patients (78.2%) were younger than 65 years. Of 206 cases, 127 (61.7%) were ultimately authorized without any change to the requested RT technique or prescription dose; 56 (27.2%) were authorized after modification to RT technique and/or prescription dose required by the payer. Of 21 cases with required prescription dose change, the median decrease in dose was 24.0 (range, 2.3-51.0) Gy. Of 202 cases (98.1%) with RT delivered, 72 (34.9%) were delayed for a mean (SD) of 7.8 (9.1) days and median of 5 (range, 1-49) days. Four cases (1.9%) ultimately did not receive any authorization, with 3 (1.5%) not undergoing RT, and 1 (0.5%) seeking treatment at another institution.

In this cohort study of patients with payer-denied cases, most insurance denials in radiation oncology were ultimately approved on appeal; however, RT technique and/or effectiveness may be compromised by payer-mandated changes. Further investigation and action to recognize the time and financial burdens on clinicians and clinical effects on patients caused by insurance denials of RT is needed.

Cancer stem cell biomarkers SRY (sex-determining region Y)-box 2 (SOX2) and octamer-binding transcription factor 4 (Oct4) account for radioresistance in cervical squamous cell cancers (CSCCs). Their clinical implications are limited and contradictory.

In this prospective cohort study, we recruited patients with FIGO IB2-IVA CSCC treated with primary chemoradiotherapy on regular follow-up. Tissue biopsy specimens were evaluated for SOX2 and Oct4 expression by immunohistochemistry, quantified by a product of proportion and intensity scores.

A total of 59 patients were included. Most had a moderately differentiated (81%), keratinizing (59%) CSCC, and ≥FIGO stage IIB disease (95%). SOX2 expression (high:low 21:38 patients) and Oct4 expression (high:low 4:55 patients) had a significant interrelation (p = 0.005, odds ratio (95% CI) - 1.23 (1.004-1.520)). At a median follow-up of 36 months, the 3-year overall survival (OS) was 60% and 53% for low and high SOX2 expression (p = 0.856), and 54% and 100% for low and high Oct4 expression (p = 0.114). The 3-year disease-frese survival (DFS) was 65% and 50% in the low and high SOX2 expression (p = 0.259), and 59% and 75% for low and high Oct4 expression (p = 0.598). SOX2 expression was the only variable significantly associated with a lower OS and DFS on regression analysis.

Our study demonstrated a trend toward improved OS and DFS with low SOX2 and high Oct4 expression in CSCC patients undergoing chemoradiotherapy.