• SBRT
• lung cancer
• re-irradiation
• stereotactic body radiotherapy

• Non-small cell lung cancer
• Residual disease
• Stereotactic body radiation therapy
• Stereotactic boost

• Guidelines
• Hypofractionated radiation
• Non-small cell lung cancer
• Oligometastasis
• Radiotherapy
• Stereotactic radiation therapy

This study evaluated the toxicity associated with radiation techniques on curative re-irradiation (re-RT) in patients with thoracic recurrence of non-small cell lung cancer (NSCLC). From 2011 to 2019, we retrospectively reviewed the data of 63 patients with salvage re-RT for in-field or marginal recurrence of NSCLC at two independent institutions. Re-RT techniques using X-ray beams and proton beam therapy (PBT) were also included. Re-RT had a 2-year overall survival (OS) and local progression-free survival of 48.0% and 52.0%, respectively. Fifteen patients experienced grade 3 or higher toxicity after re-RT. The complication rates were 18.2% (4/22) and 26.8% (11/41) in PBT patients and X-ray patients, respectively. Airway or esophageal fistulas occurred in seven patients (11.1%). Fistulas or severe airway obstruction occurred in patients with tumors adjacent to the proximal bronchial tree and esophagus, who underwent hypofractionated radiotherapy (RT) or concurrent chemotherapy, and with a higher dose exposure to the esophagus. In conclusion, salvage re-RT was feasible even in patients with local recurrence within the previous RT field. PBT showed similar survival outcomes and toxicity to those of other techniques. However, thoracic re-RT should be performed carefully considering tumor location and RT regimens such as the fraction size and concurrent chemotherapy.

• Carcinoma, Non-Small-Cell Lung/radiotherapy
• Humans
• Lung Neoplasms/radiotherapy
• Neoplasm Recurrence, Local/radiotherapy
• Re-Irradiation

• 28990 Cancer Research UK

Patients with non-small-cell lung cancer (NSCLC) frequently develop radioresistance, resulting in poor response to radiation and unfavourable prognosis. Early detection of radioresistance hence can guide the adjustment of treatment regimens in time. Exosomes are lipid bilayer-enclosed vesicles with sub-micrometer size that are released by various cells. Exosomes contain a tissue-specific signature wherein a variety of proteins and nucleic acids are selectively packaged. Growing evidence shows exosomes are involved in cancer pathophysiology and exosomes as the latest addition to the liquid biopsy portfolio have been used in cancer diagnosis. Compared to cell free RNA, exosomal lipid envelope can effectively protect RNA cargo against degradation. Therefore, exosomes may hold great promise for the identification of radioresistance. Here, we report six plasma exosomal miRNAs could be used to distinguish radioresistant NSCLC patients from radiosensitive NSCLC patients and to evaluate the prognosis of NSCLC. Samples were obtained from 52 NSCLC patients with or without radioresistance and 45 age-matched healthy volunteers. Exosomes in 1 ml plasma were isolated followed by extraction of small RNA. The expression levels of miRNAs were determined by quantitative real-time PCR. Potential miRNA markers were further evaluated in additional 52 NSCLC patients. We found exosomal miR-1246 and miR-96 are significantly overexpressed in NSCLC patients. Moreover, exosomal miR-96 in patients with radioresistant NSCLC is significantly higher than that of controls. Exosomal miR-96 also demonstrates a significant correlation with vascular invasion and poor overall survival. Altogether, our results indicate that exosomal miR-96 could be a non-invasive diagnostic and prognostic marker of radioresistant NSCLC.

The population of cancer patients with second primary malignancies (SPMs) is rapidly growing. The relationship between radiotherapy and SPMs for some types of tumors is unknown or debated. In this study, we identify 24 types of first primary malignancies (FPMs) between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Patients in the radiotherapy group were matched to those in the no radiotherapy group with a matching ratio of 1:1. After propensity-score matching (PSM), additional competing risk regression analyses were performed to calculate the efficacy of radiotherapy to SPMs in the PSM-adjusted population. In addition, the Fine and Gray model was utilized in the primary cohorts, and stratified analyses were performed based on surgery. This study includes a total of 2,831,789 eligible patients with tumors diagnosed from 2004 to 2015 in the SEER 18 database, amongst whom 100,194 (3.5%) patients developed SPMs. We observe higher risks of SPMs associated with radiotherapy in several types of tumors in the PSM-adjusted populations (small bowel adenocarcinoma, small cell lung carcinoma, prostate adenocarcinoma, urinary bladder transitional cell carcinoma, invasive ductal breast carcinoma, invasive lobular breast carcinoma, and Hodgkin lymphoma). The results in the PSM-adjusted populations were consistent with outcomes in the multivariable competing risk models. Meanwhile, in subgroup analyses stratified by surgery, some other types of tumor (except for those with positive results in the PSM-adjusted cohorts) with radiotherapy were also associated with a higher prevalence of SPMs in the subgroups of surgical treatment (pancreatic adenocarcinoma, rectal adenocarcinoma, lung adenocarcinoma and follicular thyroid carcinoma in the surgery subgroups). The impact of radiotherapy on the incidence of secondary malignancies is distinct in different types of cancer. These findings merit further investigation and may ultimately impact treatment decision-making for tumor management.

• first primary malignancies
• pan-cancer
• radiotherapy
• second primary malignancies

• Esophageal cancer
• lung cancer
• mediastinal lymphoma
• mesothelioma
• proton therapy
• radiotherapy
• thoracic
• thymic cancer

• Humans
• Neoplasm Recurrence, Local/radiotherapy
• Proton Therapy
• Re-Irradiation/adverse effects
• Re-Irradiation/methods

• R50 CA275877 NCI NIH HHS

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Non-Small-Cell Lung/mortality
• Carcinoma, Non-Small-Cell Lung/pathology
• Carcinoma, Non-Small-Cell Lung/therapy
• Chemoradiotherapy/methods
• Chemoradiotherapy/mortality
• Disease-Free Survival
• Female
• Humans
• Lung Neoplasms/mortality
• Lung Neoplasms/pathology
• Lung Neoplasms/therapy
• Male
• Middle Aged
• Neoplasm Recurrence, Local/mortality
• Neoplasm Recurrence, Local/pathology
• Retrospective Studies
• Salvage Therapy/methods
• Salvage Therapy/mortality
• Treatment Outcome

• Small cell lung cancer (SCLC)
• outcome
• prognostic factor
• recurrence
• reirradiation

• CTC
• LA-NSCLC
• Lung cancer
• Prospective trial
• Radiation oncology

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Non-Small-Cell Lung/diagnosis
• Carcinoma, Non-Small-Cell Lung/pathology
• Carcinoma, Non-Small-Cell Lung/therapy
• Cell Count/methods
• Chemoradiotherapy
• Feasibility Studies
• Female
• Humans
• Lung Neoplasms/diagnosis
• Lung Neoplasms/pathology
• Lung Neoplasms/therapy
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Neoplasm Staging
• Neoplastic Cells, Circulating/pathology

• K08 NS076548 NINDS NIH HHS
• R01 CA201071 NCI NIH HHS

To present a systematic approach to the reirradiation special medical physics consult (ReRT-SMPC) process.

An in-house reirradiation committee of physicians and physicists was formed to develop a streamlined and well-documented approach to ReRT-SMPCs. Dosimetric goals and considerations for tissue repair were generated by the committee with input from the literature, clinical trial guidelines, and physician experience. Procedural workflow was also defined.

The total number of ReRT-SMPCs performed in our department in 2018 was 401, corresponding to 369 unique patients and 16% of the total number of patients receiving external beam radiation in our department that year. This constituted a large increase over the 183 ReRT-SMPCs performed in 2017. We have found that a standardized ReRT-SMPC workflow helps to safeguard patients, documents the clinical decision-making process for medical and legal purposes, and facilitates the peer-review process. The data being collected from each consult along with toxicity and outcomes data can be used to help inform future re-treatment guidelines.

As the number of patients returning for additional courses of radiation continues to increase, a uniform method for the ReRT-SMPC workflow and analysis is a powerful tool for ensuring patient safety, understanding and predicting treatment toxicity, and refining reirradiation dosimetric limits.

• non-small cell lung cancer
• pencil beam scanning
• proton therapy
• radiation therapy
• toxicities

• Animals
• Carcinoma, Non-Small-Cell Lung/mortality
• Carcinoma, Non-Small-Cell Lung/pathology
• Carcinoma, Non-Small-Cell Lung/radiotherapy
• Humans
• Lung Neoplasms/mortality
• Lung Neoplasms/pathology
• Lung Neoplasms/radiotherapy
• Neoplasm Staging
• Proton Therapy/adverse effects
• Proton Therapy/mortality
• Risk Factors
• Treatment Outcome