Longitudinal quality of life after sublobar resection and stereotactic body radiation therapy for early-stage non-small cell lung cancer.

BACKGROUND: Many patients with early-stage lung cancer are not candidates for lobectomy because of various factors, with treatment options including sublobar resection or stereotactic body radiation therapy (SBRT). Limited information exists regarding patient-centered outcomes after these treatments. METHODS: Subjects with stage I-IIA non-small cell lung cancer (NSCLC) at high risk for lobectomy who underwent treatment with sublobar resection or SBRT were recruited from five medical centers. Quality of life (QOL) was compared with the Short Form 8 (SF-8) for physical and mental health and Functional Assessment of Cancer Therapy-Lung (FACT-L) surveys at baseline (pretreatment) and 7 days, 30 days, 6 months, and 12 months after treatment. Propensity score methods were used to control for confounders. RESULTS: Of 337 subjects enrolled before treatment, 63% received SBRT. Among patients undergoing resection, 89% underwent minimally invasive video-assisted thoracic surgery or robot-assisted resection. Adjusted analyses showed that SBRT-treated patients had both higher physical health SF-8 scores (difference in differences [DID], 6.42; p = .0008) and FACT-L scores (DID, 2.47; p = .004) at 7 days posttreatment. Mental health SF-8 scores were not different at 7 days (p = .06). There were no significant differences in QOL at other time points, and all QOL scores returned to baseline by 12 months for both groups. CONCLUSIONS: SBRT is associated with better QOL immediately posttreatment compared with sublobar resection. However, both treatment groups reported similar QOL at later time points, with a return to baseline QOL. These findings suggest that sublobar resection and SBRT have a similar impact on the QOL of patients with early-stage lung cancer deemed ineligible for lobectomy.

Adverse Events Following Limited Resection versus Stereotactic Body Radiation Therapy for Early Stage Lung Cancer.

Rationale: Approximately a quarter of patients with early stage lung cancer are not medically fit for lobectomy. Limited resection and stereotactic body radiation therapy (SBRT) have emerged as alternatives for these patients. Given the equipoise on the effectiveness of the two treatments, treatment-related adverse events (AEs) could have a significant impact on patients' decision-making and treatment outcomes. Objectives: To compare the AE profile between SBRT versus limited resection. Methods: Data were derived from a prospective cohort of patients with stage I-IIA non-small cell lung cancer who were deemed as high-risk for lobectomy recruited from five centers across the United States. Propensity scores and inverse probability weighting were used to compare the rates of 30- and 90-day AEs among patients treated with limited resection versus SBRT. Results: Overall, 65% of 252 patients underwent SBRT. After adjusting for propensity scores, there was no significant difference in developing at least one AE comparing SBRT to limited resection (odds ratio [OR]: 1.00; 95% confidence interval [CI]: 0.65-1.55 and OR: 1.27; 95% CI: 0.84-1.91 at 30 and 90 days, respectively). SBRT was associated with lower risk of infectious AEs than limited resection at 30 days (OR: 0.05; 95% CI: 0.01-0.39) and 90 days posttreatment (OR: 0.41; 95% CI: 0.17-0.98). Additionally, SBRT was associated with persistently elevated risk of fatigue (OR: 2.47; 95% CI: 1.34-4.54 at 30 days and OR: 2.69; 95% CI: 1.52-4.77 at 90 days, respectively), but significantly lower risks of respiratory AEs (OR: 0.36; 95% CI: 0.20-0.65 and OR: 0.51; 95% CI: 0.31-0.86 at 30 and 90 days, respectively). Conclusions: Though equivalent in developing at least one AE, we found that SBRT is associated with less toxicity than limited resection in terms of infectious and respiratory AEs but higher rates of fatigue that persisted up to 3 months posttreatment. This information, combined with data about oncologic effectiveness, can help patients' decision-making regarding these alternative therapies.

Cancer healthcare disparities among African Americans in the United States.

A need exists to examine racial disparities in the healthcare arena and the impact on patients with cancer. Despite ongoing efforts to increase equity in primary healthcare access, racial and socioeconomic disparities persist, thus contributing to disproportionate treatment outcomes and survivorship among minority and low-income patients. Such disparities have been revealed in treatment cohorts of patients with multiple forms of cancer, including breast, cervical, ovarian, endometrial, prostate, lung, colorectal, gastrointestinal, and hepatocellular, and have been attributed to a range of co-occurring behavioral, social determinants of health, underlying genetic factors, as well as access to educational opportunities that limit the quality of informed healthcare. These various interrelated factors widen cancer healthcare disparities synergistically throughout underserved communities, and their influence has been amplified by the coronavirus disease 2019 (COVID-19) pandemic. Fundamentally, a lack of basic and clinical research exists that fails to adequately reflect diversity and minority involvement in drug development. Although overcoming the obstacles responsible for chronic treatment disparities is a formidable task, promising means of achieving more uniform quality healthcare are becoming more clearly elucidated. To reduce disease progression, increase overall survival, and improve the health of vulnerable populations, it is necessary to identify and fully disclose environmental, biological, and ancestral factors that impact the risk for cancer; heal historical fractures within communities; and increase participation of racial and ethnic minorities in screening efforts and research studies. This requires developing a system of justice and trust based on specific, solution-oriented grassroots community efforts working in tandem with medical and pharmaceutical leaders. By fully exploring and pinpointing the underlying causes of healthcare disparities, it should be possible to define strategies and interventions most likely to transform cancer care. The ultimate goal is understanding individual, cultural, and biological vulnerabilities, including environmental and epigenetic liabilities, to optimize cancer prevention, diagnosis, and treatment.

Cancer Disparities and Health Equity: A Policy Statement From the American Society of Clinical Oncology.

ASCO strives, through research, education, and promotion of the highest quality of patient care, to create a world where cancer is prevented and every survivor is healthy. In this pursuit, cancer health equity remains the guiding institutional principle that applies to all its activities across the cancer care continuum. In 2009, ASCO committed to addressing differences in cancer outcomes in its original policy statement on cancer disparities. Over the past decade, despite novel diagnostics and therapeutics, together with changes in the cancer care delivery system such as passage of the Affordable Care Act, cancer disparities persist. Our understanding of the populations experiencing disparate outcomes has likewise expanded to include the intersections of race/ethnicity, geography, sexual orientation and gender identity, sociodemographic factors, and others. This updated statement is intended to guide ASCO's future activities and strategies to achieve its mission of conquering cancer for all populations. ASCO acknowledges that much work remains to be done, by all cancer stakeholders at the systems level, to overcome historical momentum and existing social structures responsible for disparate cancer outcomes. This updated statement affirms ASCO's commitment to moving beyond descriptions of differences in cancer outcomes toward achievement of cancer health equity, with a focus on improving equitable access to care, improving clinical research, addressing structural barriers, and increasing awareness that results in measurable and timely action toward achieving cancer health equity for all.

Health Insurance Coverage Disruptions and Cancer Care and Outcomes: Systematic Review of Published Research.

BACKGROUND: Lack of health insurance coverage is associated with poor access and receipt of cancer care and survival in the United States. Disruptions in coverage are common among low-income populations, but little is known about associations of disruptions with cancer care, including prevention, screening, and treatment, as well as outcomes of stage at diagnosis and survival. METHODS: We conducted a systematic review of studies of health insurance coverage disruptions and cancer care and outcomes published between 1980 and 2019. We used the PubMed, EMBASE, Scopus, and CINAHL databases and identified 29 observational studies. Study characteristics and key findings were abstracted and synthesized qualitatively. RESULTS: Studies evaluated associations between coverage disruptions and prevention or screening (31.0%), treatment (13.8%), end-of-life care (10.3%), stage at diagnosis (44.8%), and survival (20.7%). Coverage disruptions ranged from 4.3% to 32.8% of patients age-eligible for breast, cervical, or colorectal cancer screening. Between 22.1% and 59.5% of patients with Medicaid gained coverage only at or after cancer diagnosis. Coverage disruptions were consistently statistically significantly associated with lower receipt of prevention, screening, and treatment. Among patients with cancer, those with Medicaid disruptions were statistically significantly more likely to have advanced stage (odds ratios = 1.2-3.8) and worse survival (hazard ratios = 1.28-2.43) than patients without disruptions. CONCLUSIONS: Health insurance coverage disruptions are common and adversely associated with receipt of cancer care and survival. Improved data infrastructure and quasi-experimental study designs will be important for evaluating the associations of federal and state policies on coverage disruptions and care and outcomes.

Phase I/II trial of nano-camptothecin CRLX101 with capecitabine and radiotherapy as neoadjuvant treatment for locally advanced rectal cancer.

CRLX101 is a nanoparticle-drug conjugate with a camptothecin payload. We assessed the toxicity and pathologic complete response (pCR) rate of CRLX101 with standard neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer. A single-arm study was conducted with a 3 + 3 dose escalation phase Ib followed by phase II at the maximum tolerated dose (MTD). Thirty-two patients were enrolled with 29 (91%) patients having T3/4 and 26 (81%) N1/2 disease. In phase Ib, no patient experienced a dose limiting toxicity (DLT) with every other week dosing, while 1/9 patients experienced a DLT with weekly dosing. The weekly MTD was identified as 15 mg/m2. The most common grade 3-4 toxicity was lymphopenia, with only 1 grade 4 event. pCR was achieved in 6/32 (19%) patients overall and 2/6 (33%) patients at the weekly MTD. CRLX101 at 15 mg/m2 weekly with neoadjuvant CRT is a feasible combination strategy with an excellent toxicity profile. Clinicaltrials.gov registration NCT02010567.

Use of non-ionizing electromagnetic fields for the treatment of cancer.

Cancer treatment and treatment options are quite limited in circumstances such as when the tumor is inoperable, in brain cancers when the drugs cannot penetrate the blood-brain-barrier, or when there is no tumor-specific target for generation of effective therapeutic antibodies. Despite the fact that electromagnetic fields (EMF) in medicine have been used for therapeutic or diagnostic purposes, the use of non-ionizing EMF for cancer treatment is a new emerging concept. Here we summarize the history of EMF from the 1890's to the novel and new innovative methods that target and treat cancer by non-ionizing radiation.

Mutational Landscapes of Smoking-Related Cancers in Caucasians and African Americans: Precision Oncology Perspectives at Wake Forest Baptist Comprehensive Cancer Center.

Background: Cancers related to tobacco use and African-American ancestry are under-characterized by genomics. This gap in precision oncology research represents a major challenge in the health disparities in the United States. Methods: The Precision Oncology trial at the Wake Forest Baptist Comprehensive Cancer Center enrolled 431 cancer patients from March 2015 to May 2016. The composition of these patients consists of a high representation of tobacco-related cancers (e.g., lung, colorectal, and bladder) and African-American ancestry (13.5%). Tumors were sequenced to identify mutations to gain insight into genetic alterations associated with smoking and/or African-American ancestry. Results: Tobacco-related cancers exhibit a high mutational load. These tumors are characterized by high-frequency mutations in TP53, DNA damage repair genes (BRCA2 and ATM), and chromatin remodeling genes (the lysine methyltransferases KMT2D or MLL2, and KMT2C or MLL3). These tobacco-related cancers also exhibit augmented tumor heterogeneities. Smoking related genetic mutations were validated by The Cancer Genome Atlas dataset that includes 2,821 cases with known smoking status. The Wake Forest and The Cancer Genome Atlas cohorts (431 and 7,991 cases, respectively) revealed a significantly increased mutation rate in the TP53 gene in the African-American subgroup studied. Both cohorts also revealed 5 genes (e.g. CDK8) significantly amplified in the African-American population. Conclusions: These results provide strong evidence that tobacco is a major cause of genomic instability and heterogeneity in cancer. TP53 mutations and key oncogene amplifications emerge as key factors contributing to cancer outcome disparities among different racial/ethnic groups.

Circulating mutational portrait of cancer: manifestation of aggressive clonal events in both early and late stages.

BACKGROUND: Solid tumors residing in tissues and organs leave footprints in circulation through circulating tumor cells (CTCs) and circulating tumor DNAs (ctDNA). Characterization of the ctDNA portraits and comparison with tumor DNA mutational portraits may reveal clinically actionable information on solid tumors that is traditionally achieved through more invasive approaches. METHODS: We isolated ctDNAs from plasma of patients of 103 lung cancer and 74 other solid tumors of different tissue origins. Deep sequencing using the Guardant360 test was performed to identify mutations in 73 clinically actionable genes, and the results were associated with clinical characteristics of the patient. The mutation profiles of 37 lung cancer cases with paired ctDNA and tumor genomic DNA sequencing were used to evaluate clonal representation of tumor in circulation. Five lung cancer cases with longitudinal ctDNA sampling were monitored for cancer progression or response to treatments. RESULTS: Mutations in TP53, EGFR, and KRAS genes are most prevalent in our cohort. Mutation rates of ctDNA are similar in early (I and II) and late stage (III and IV) cancers. Mutation in DNA repair genes BRCA1, BRCA2, and ATM are found in 18.1% (32/177) of cases. Patients with higher mutation rates had significantly higher mortality rates. Lung cancer of never smokers exhibited significantly higher ctDNA mutation rates as well as higher EGFR and ERBB2 mutations than ever smokers. Comparative analysis of ctDNA and tumor DNA mutation data from the same patients showed that key driver mutations could be detected in plasma even when they were present at a minor clonal population in the tumor. Mutations of key genes found in the tumor tissue could remain in circulation even after frontline radiotherapy and chemotherapy suggesting these mutations represented resistance mechanisms. Longitudinal sampling of five lung cancer cases showed distinct changes in ctDNA mutation portraits that are consistent with cancer progression or response to EGFR drug treatment. CONCLUSIONS: This study demonstrates that ctDNA mutation rates in the key tumor-associated genes are clinical parameters relevant to smoking status and mortality. Mutations in ctDNA may serve as an early detection tool for cancer. This study quantitatively confirms the hypothesis that ctDNAs in circulation is the result of dissemination of aggressive tumor clones and survival of resistant clones. This study supports the use of ctDNA profiling as a less-invasive approach to monitor cancer progression and selection of appropriate drugs during cancer evolution.

Image guided radiation therapy may result in improved local control in locally advanced lung cancer patients.

PURPOSE: Image guided radiation therapy (IGRT) is designed to ensure accurate and precise targeting, but whether improved clinical outcomes result is unknown. METHODS AND MATERIALS: A retrospective comparison of locally advanced lung cancer patients treated with and without IGRT from 2001 to 2012 was conducted. Median local failure-free survival (LFFS), regional, locoregional failure-free survival (LRFFS), distant failure-free survival, progression-free survival, and overall survival (OS) were estimated. Univariate and multivariate models assessed the association between patient- and treatment-related covariates and local failure. RESULTS: A total of 169 patients were treated with definitive radiation therapy and concurrent chemotherapy with a median follow-up of 48 months in the IGRT cohort and 96 months in the non-IGRT cohort. IGRT was used in 36% (62 patients) of patients. OS was similar between cohorts (2-year OS, 47% vs 49%, P = .63). The IGRT cohort had improved 2-year LFFS (80% vs 64%, P = .013) and LRFFS (75% and 62%, P = .04). Univariate analysis revealed IGRT and treatment year improved LFFS, whereas group stage, dose, and positron emission tomography/computed tomography planning had no impact. IGRT remained significant in the multivariate model with an adjusted hazard ratio of 0.40 (P = .01). Distant failure-free survival (58% vs 59%, P = .67) did not differ significantly. CONCLUSION: IGRT with daily cone beam computed tomography confers an improvement in the therapeutic ratio relative to patients treated without this technology.

Reassessment of the role of enteral tube feedings for patients with esophageal cancer.

Nutrition is important for patients with esophageal cancer because dysphagia can be exacerbated by chemoradiotherapy. Some centers suggest routine enteral tube placement (TF) to facilitate nutrition. This investigation was to evaluate the use of TF access for patients undergoing multimodality therapy for esophageal carcinoma. This retrospective study analyzed 113 patients who underwent esophagectomy and 97 patients who underwent definition chemoradiotherapy for esophageal cancer between 2001 and 2013. Throughout this time period, a strategy for selective tube placement was used. Nutrition was assessed through absolute lymphocyte counts, protein, and albumin levels. A total of 28 (30%) patients during preoperative chemoradiotherapy and 31 (32%) of those undergoing definitive chemoradiation received TFs. There were 16 Dobhoff tubes, 28 gastrostomy tubes, and 15 jejunostomies. Tubes were maintained an average of 3.9 months with 20 (34%) of these patients reporting tube-related complications. At the time of surgery, there was no statistical difference in any of the nutritional assessments between those patients who received TF and those who did not. Both groups experienced similar total postoperative complication rates (64% vs 65%) and similar median length of hospital stay (12 to 13 days). Chemoradiotherapy resulted in decreased nutritional parameters; however, there was no difference in the degree of reduction between those who underwent TF and those who did not. The data show that routine placement of enteral access is not necessary for esophageal carcinoma. In fact, the risks of placing enteral access may outweigh the benefits. Administration of TF should be restricted to select patients during chemoradiotherapy or before esophagectomy.

F10 Inhibits Growth of PC3 Xenografts and Enhances the Effects of Radiation Therapy.

Chemotherapy remains of limited use for the treatment of prostate cancer with only one drug, docetaxel, demonstrating a modest survival advantage for treatment of late-stage disease. Data from the NCI 60 cell line screen indicated that the castration-resistant prostate cancer cell lines PC3 and DU145 were more sensitive than average to the novel polymeric fluoropyrimidine (FP), F10, despite displaying less than average sensitivity to the widely-used FP, 5FU. Here, we show that F10 treatment of PC3 xenografts results in a significant survival advantage (treatment to control ratio (T/C) days = 18; p < 0.001; n = 16) relative to control mice treated with saline. F10 (40 mg/kg/dose) was administered via jugular vein catheterization 3-times per week for five weeks. This aggressive dosing regimen was completed with no drug-induced weight loss and with no evidence of toxicity. F10 was also shown to sensitize PC3 cells to radiation and F10 was also shown to be a potent radiosensitizer of PC3 xenografts in vivo with F10 in combination with radiation resulting in significantly greater regression of PC3 xenografts than radiation alone. The results indicate that F10 in this pre-clinical setting is an effective chemotherapeutic agent and possesses significant radiosensitizing properties.

The role of alveolar epithelium in radiation-induced lung injury.

Pneumonitis and fibrosis are major lung complications of irradiating thoracic malignancies. In the current study, we determined the effect of thoracic irradiation on the lungs of FVB/N mice. Survival data showed a dose-dependent increase in morbidity following thoracic irradiation with single (11-13 Gy) and fractionated doses (24-36 Gy) of (137)Cs γ-rays. Histological examination showed a thickening of vessel walls, accumulation of inflammatory cells, collagen deposition, and regional fibrosis in the lungs 14 weeks after a single 12 Gy dose and a fractionated 30 Gy dose; this damage was also seen 5 months after a fractionated 24 Gy dose. After both single and fractionated doses, i] aquaporin-5 was markedly decreased, ii] E-cadherin was reduced and iii] prosurfactant Protein C (pro-SP-c), the number of pro-SP-c(+) cells and vimentin expression were increased in the lungs. Immunofluorescence analysis revealed co-localization of pro-SP-c and α-smooth muscle actin in the alveoli after a single dose of 12 Gy. These data suggest that, i] the FVB/N mouse strain is sensitive to thoracic radiation ii] aquaporin-5, E-cadherin, and pro-SP-c may serve as sensitive indicators of radiation-induced lung injury; and iii] the epithelial-to-mesenchymal transition may play an important role in the development of radiation-induced lung fibrosis.

ACR appropriateness criteria® resectable rectal cancer.

The management of resectable rectal cancer continues to be guided by clinical trials and advances in technique. Although surgical advances including total mesorectal excision continue to decrease rates of local recurrence, the management of locally advanced disease (T3-T4 or N+) benefits from a multimodality approach including neoadjuvant concomitant chemotherapy and radiation. Circumferential resection margin, which can be determined preoperatively via MRI, is prognostic. Toxicity associated with radiation therapy is decreased by placing the patient in the prone position on a belly board, however for patients who cannot tolerate prone positioning, IMRT decreases the volume of normal tissue irradiated. The use of IMRT requires knowledge of the patterns of spreads and anatomy. Clinical trials demonstrate high variability in target delineation without specific guidance demonstrating the need for peer review and the use of a consensus atlas. Concomitant with radiation, fluorouracil based chemotherapy remains the standard, and although toxicity is decreased with continuous infusion fluorouracil, oral capecitabine is non-inferior to the continuous infusion regimen. Additional chemotherapeutic agents, including oxaliplatin, continue to be investigated, however currently should only be utilized on clinical trials as increased toxicity and no definitive benefit has been demonstrated in clinical trials. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria: local excision in early-stage rectal cancer.

Low anterior resection or abdominoperineal resection is considered standard treatment for early rectal cancer. These procedures, however, carry a risk of morbidity and mortality that may not be warranted for early distal lesions, which may be treated with local excision. Emerging data has investigated the efficacy of local excision in patients with early stage rectal cancers. An expert panel designated by the American College of Radiology has reviewed supporting data, from a few prospective multi-institutional trials and a number of single-institution, retrospective reviews. The consensus recognizes the importance of accurate staging to identify patients who may be candidates for a local excision approach. Optimal candidates for local excision alone include small, low-lying T1 tumors, without adverse pathologic features. A number of procedures may be safely used including transanal, posterior trans-sphincteric, posterior proctotomy, transanal excision, or transanal microsurgery. It is important to note that none of these include lymph node evaluation, and depending on the risk of lymph node metastases, adjuvant radiation with or without chemotherapy may be warranted. Patients with positive margins or T3 lesions are at high risk of local recurrence and should be offered immediate APR or LAR. However, patients with high-risk T1 tumors, T2 tumors, or those who are not amenable to more radical surgery may benefit from adjuvant treatment. Data have also reported excellent local control rates for neoadjuvant radiation +/- chemotherapy followed by local excision in higher risk patients, but it is not yet clear if this approach reduces recurrence rates over surgery alone.

ACR Appropriateness Criteria: rectal cancer-metastatic disease at presentation.

In 2009, an estimated 40,870 new cases of rectal cancer will be diagnosed in the USA. After decades of treating metastatic colorectal cancer (CRC) with 5-fluorouracil alone, newer agents have resulted in significant improvements in disease-free and overall survival rates. These improvements stem from combinations of newer cytotoxic agents and targeted therapies. Based on performance status and burden of disease, metastatic CRC patients are generally treated with either a curative or palliative intent. Curative paradigm patients often have low burden liver or lung metastases which are technically resectable. Patients with resectable colorectal liver metastases and no evidence of any extrahepatic metastases have impressive 5-year survival rates of 30%-70% following resection. Unfortunately, only 20%-30% of patients with colorectal liver metastases are candidates for resection at initial presentation. Patients with unresectable liver or lung metastasis are candidates for local therapies including radioablation, chemoembolization, radioembolization, and stereotactic radiation therapy. In select patients with metastatic CRC, neoadjuvant or adjuvant pelvic chemoradiation (CRT) is indicated to prevent local recurrence. Patients who have resectable metastatic disease with symptomatic, obstructive, Stage T3-4 and N1, or low-lying (

Bronchial stenosis: an underreported complication of high-dose external beam radiotherapy for lung cancer?

PURPOSE: To assess the incidence of clinically significant bronchial stenosis in patients treated with high doses (i.e., >70 Gy) of twice-daily external beam radiation therapy (RT). METHODS AND MATERIALS: The outcomes of 103 patients with unresectable non-small-cell lung cancer, treated twice daily to doses ranging from 7080 to 8640 cGy between 1992 and 2001, were analyzed. Most were treated on prospective clinical trials. For the dose-effect comparison, the patients were divided on the basis of the total dose: 67 received 74 Gy (range, 70.8-74.5 Gy; median, 73.6 Gy), 20 received 80 Gy, and 16 received 86 Gy (range, 85.2-86.4 Gy; median, 86.4 Gy). Sixty-six patients received sequential chemotherapy before RT. RT-induced bronchial stenosis was defined as symptomatic airway narrowing diagnosed by bronchoscopy or computed tomography scan without evidence of recurrent tumor in that region. RESULTS: Eight patients developed RT-induced, clinically significant, bronchial stenosis 2-48 months (median, 6 months) after RT. The 1-year and 4-year actuarial rate of stenosis was 7% and 38%, respectively. The median overall survival was 2.5 years (5 of 8 were alive at the writing of this report). A suggestion was also found of a dose-response effect with external beam radiotherapy-induced stenosis, with a rate of 4% and 25% at a dose of approximately 74 Gy and 86 Gy, respectively. CONCLUSION: Radiation therapy-induced bronchial stenosis is a significant clinical complication of dose escalation for lung cancer. This complication has been previously mentioned in the literature, but ours is the largest report to date, and the findings suggest that the risk rises with increasing dose. It is likely that this process would manifest in more patients if their disease were controlled well enough for more prolonged survival.