Curr. Oncol., Volume 27, Issue 4 (August 2020) – 21 articles

Immunotherapy has emerged as a standard of cancer treatment, with an increasing number of indications. Recently, opportunistic infections have been reported in several cases in which immunotherapy has led to an increased susceptibility to infection. The present case is the first report of cytomegalovirus (cmv) gastritis occurring in a patient with melanoma during immunotherapy without immune-related adverse events (iraes) and without the use of immunosuppressant agents. A 43-year-old woman presented with stage iii malignant melanoma. She underwent wide excision of skin, with lymph node dissection, and she started immunotherapy with a 3-week cycle of pembrolizumab. The patient demonstrated stable disease response, and no iraes were observed during her initial treatment courses. However, after the 9th treatment cycle, she began to experience epigastric pain that worsened significantly, requiring a visit to the emergency centre. Imaging by computed tomography (ct) and integrated positron-emission tomography/ct revealed severe diffuse gastroduodenitis with acute pancreatitis. Esophagogastroduodenoscopy showed diffuse oozing, hemorrhagic, edematous, and exfoliative mucosa involving the entire gastric wall, defined as acute hemorrhagic gastritis. Biopsies of the gastric wall revealed cmv infection. Those findings were consistent with a diagnosis of cmv gastritis, and the patient received antiviral therapy with ganciclovir. After treatment, she recovered enough to resume immunotherapy. This case report presents a rare occurrence of cmv gastritis related to immunotherapy. As more patients are treated with immunotherapy, incidences of cmv infections are expected to increase; a high index of clinical suspicion is therefore needed in symptomatic patients. Full article

Paraneoplastic syndromes associated with anal squamous cell carcinoma (scc) are rare. Erythema gyratum repens (egr) is a cutaneous paraneoplastic syndrome with distinctive characteristics. Here, we report the rare case of a 73-year-old woman with a chronic erythematous rash for 11 months associated with intense pruritus. She was treated with prednisone and antihistamines by dermatologists, but did not respond. The patient was subsequently seen in our clinic for unintentional weight loss and anorexia with intermittent nausea and vomiting. During further evaluation with imaging studies, upper endoscopy, and colonoscopy with biopsy, poorly differentiated anal scc was identified. Biopsies of the skin rash were characteristic of egr. She was treated using concurrent chemotherapy with 5-fluorouracil and mitomycin C and pelvic radiation (50.4 Gy in 28 fractions) for anal scc. She tolerated the treatment, and her rash faded, with resolution of the pruritus. Full article

Because of the global coronavirus pandemic, the 2020 annual scientific meeting of the American Society of Clinical Oncology took place virtually, 29–30 May. At the meeting, results from key studies about the treatment of chronic lymphocytic leukemia (cll) were disseminated. Studies examined the efficacy and safety of ibrutinib, acalabrutinib, zanubrutinib, and venetoclax as monotherapy or in combination with novel agents for patients with treatment-naïve and relapsed or refractory cll. Our meeting report describes the foregoing studies and presents interviews with investigators and commentaries by Canadian hematologists about potential effects on Canadian practice. Full article

Background: Despite universal access to health care in Canada, disparities relating to social determinants of health contribute to discrepancies in cancer incidence and outcomes between rural and urban areas. Given that Canada has one of the highest-quality national population-based cancer registry systems in the world and little information is available about cancer statistics specific to northwestern Ontario, the purpose of this study was to estimate the percentage of cancer patients without documentation of a specialist consultation (medical or radiation oncology consultation) and to determine factors that affect access to specialist consultation in northwestern Ontario. Methods: This population-based retrospective study used administrative data obtained through the Ontario Cancer Data Linkage Project. For each index case, a timeline was constructed of all Ontario Health Insurance Plan billing codes and associated service dates, starting with the primary cancer diagnosis and ending with death. Specific factors affecting access to specialist consultation were assessed. Results: Within the 6-year study period (2010–2016), 2583 index cases were identified. Most (n=2007, 78%) received a specialist consultation. Factors associated with not receiving a specialist consultation included older age [p<0.0001; odds ratio (or): 0.29; 95% confidence interval (ci): 0.19 to 0.44] and rural residence (p<0.0001; or: 0.48; 95% ci: 0.48 to 0.72). Factors associated with receiving a specialist consultation included increased duration of disease (p<0.0001; or: 1.32; 95% ci: 1.19 to 1.46), a diagnosis of breast cancer (p<0.0001; or: 2.51; 95% ci: 1.43 to 4.42), and a diagnosis of lung cancer (p<0.0001; or: 1.77; 95% ci: 1.38 to 2.26). Conclusions: This study is the first to look at care access in northwestern Ontario. The complexity and multidisciplinary nature of cancer care make the provision of appropriate care a challenge; a one-size-fits-all disease prevention and treatment strategy might not be appropriate. Full article

Non-melanoma skin cancers are the most prevalent form of cancer, with cutaneous squamous cell carcinoma (cSCC) being the 2nd most common type. Patients presenting with high-risk lesions associated with locally advanced or metastatic cSCC face high rates of recurrence and mortality. Accurate staging and risk stratification for patients can be challenging because no system is universally accepted, and no Canadian guidelines currently exist. Patients with advanced cSCC are often deemed ineligible for either or both of curative surgery and radiation therapy (RT) and, until recently, were limited to off-label systemic cisplatin–fluorouracil or cetuximab therapy, which offers modest clinical benefits and potentially severe toxicity. A new systemic therapy, cemiplimab, has been approved for the treatment of locally advanced and metastatic cSCC. In the present review, we provide recommendations for patient classification and staging based on current guidelines, direction for determining patient eligibility for surgery and RT, and an overview of the available systemic treatment options for advanced cSCC and of the benefits of a multidisciplinary approach to patient management. Full article

Introduction: Colorectal cancer is one of the most common cancers in Ontario and imposes a high burden on many Indigenous populations. There are two aims for this short communication: (1) Highlight colorectal risk factor findings from a population-based case–control study; (2) Highlight trends and challenges of colorectal cancer research in Indigenous populations in Ontario. Methods: Prevalences of cigarette smoking, obesity, fruit and vegetable consumption, and family history of colorectal cancer were estimated using the Indigenous identifier in the Ontario Familial Colon Cancer Registry for 1999–2007 and then compared for cases and controls using age-adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Results: The registry search identified 66 Indigenous cases and 23 Indigenous controls. Cigarette smoking (OR: 1.88; 95% CI: 0.63 to 5.60) and obesity (OR: 2.16; 95% CI: 0.72 to 6.46) were higher in cases, but not statistically significantly so. Conclusions: Findings were consistent with previous literature describing Indigenous populations. A small sample size and poor Indigenous identification questions make it challenging to comprehensively understand cancer risk factors and burden in Indigenous populations. Full article

Background: Despite initial promising results, the IMvigor211 clinical trial failed to demonstrate an overall survival (OS) benefit for atezolizumab compared with chemotherapy as second-line treatment for metastatic bladder cancer (mBC). However, given lessened adverse events (AES) and preserved quality of life (QOL) with atezolizumab, there might still be investment value. To evaluate that potential value, we conducted a cost–utility analysis (CUA) of atezolizumab compared with chemotherapy from the perspective of the Canadian health care payer. Methods: A partitioned survival model was used to evaluate atezolizumab compared with chemotherapy over a lifetime horizon (5 years). The base-case analysis was conducted for the intention-to-treat (ITT) population, with additional scenario analyses for subgroups by IMvigor-defined PD-L1 status. Health outcomes were evaluated through life–year gains and quality-adjusted life–years (QALYS). Cost estimates in 2018 Canadian dollars for systemic treatment, AES, and end-of-life care were incorporated. The incremental cost-effectiveness ratio (ICER) was used to compare treatment strategies. Parameter and model uncertainty were assessed through sensitivity and scenario analyses. Per Canadian guidelines, cost and effectiveness were discounted at 1.5%. Results: For the ITT population, the expected qalys for atezolizumab and chemotherapy were 0.75 and 0.56, with expected costs of $90,290 and $8,466 respectively. The resultant ICER for atezolizumab compared with chemotherapy was $430,652 per QALY. Scenario analysis of patients with PD-L1 expression levels of 5% or greater led to a lower ICER ($334,387 per QALY). Scenario analysis of observed compared with expected benefits demonstrated a higher icer, with a shorter time horizon ($928,950 per QALY). Conclusions: Despite lessened aes and preserved QOL, atezolizumab is not considered cost-effective for the second-line treatment of mbc. Full article

Background：Breast assessment sites (bass) were developed to provide expedited and coordinated care for patients being evaluated for breast cancer (bca) in Ontario. We compared the diagnostic and treatment intervals for patients diagnosed at a bas and for those diagnosed through a usual care (uc) route. Methods: This population-based, cross-sectional study of patients diagnosed with bca in Ontario during 2007–2015 used linked administrative data. “Diagnostic interval” was the time from the earliest cancer-related health care encounter before diagnosis to diagnosis; “treatment interval” was the time from diagnosis to treatment. Diagnosis at a (bas was determined from the patient’s biopsy and mammography institutions. Interval lengths for the (bas and uc groups were compared using multivariable quantile regression, stratified by detection method. Results: The diagnostic interval was shorter for patients who were (bas-diagnosed than for those who were uc-diagnosed, with adjusted median differences of −4.0 days [95% confidence interval (ci): −3.2 days to −4.9 days] for symptomatic patients and −5.4 days (95% ci: −4.7 days to −6.1 days) for screen-detected patients. That association was modified by stage at diagnosis, with larger differences in patients with early-stage cancers. In contrast, the treatment interval was longer in patients who were (bas-diagnosed than in those who were uc-diagnosed, with adjusted median differences of 4.2 days (95% ci: 3.8 days to 4.7 days) for symptomatic patients and 4.2 days (95% ci: 3.7 days to 4.8 days) for screen-detected patients. Conclusions: Diagnosis of bca through a (bas was associated with a shorter diagnostic interval, but a longer treatment interval. Although efficiencies in the diagnostic interval might help to reduce distress experienced by patients, the longer treatment intervals for patients who are (bas-diagnosed remain a cause for concern. Full article

Background: This study compared the odds of self-reported and objectively measured cardiovascular (cv) risk factors in a sample of Canadian cancer survivors and individuals without cancer. Methods: A nationally representative sample of 45- to 85-year-old cancer survivors (n = 6288) in the Canadian Longitudinal Study on Aging were compared with individuals without cancer (n = 44,051). Results: The most prevalent risk factors in cancer survivors were all self-reported or easily measured in clinic: overweight or obesity (68.0%), former smoking (62.9%), fewer than 5 daily servings of fruits and vegetables (59.8%), hypertension (43.7%), and high waist circumference (47.0%). After adjustment for sex and education, the odds ratios of several cv risk factors varied by age in cancer survivors and the non-cancer controls. At ages 50 and 60, cancer survivors have increased odds of overweight or obesity, former smoking, hypertension, high waist circumference and truncal fat, diabetes, lung disease, and heart rate greater than 80 bpm compared with non-cancer controls. At age 70, odds did not differ for many risk factors; at age 80, no differences were evident. Without modification by age, low physical activity was more prevalent in cancer survivors (odds ratio: 1.27; 95% confidence interval: 1.17 to 1.39). There were no differences in the odds of cv risk factors measured by specialized equipment, including electrocardiography, carotid ultrasonography, spirometry, and dual-energy X-ray absorptiometry. Conclusions: The odds of several easy-to-assess cv disease risk factors are higher among middle-aged, but not older, cancer survivors relative to the general Canadian population. Initial assessment of cv risk for middle-aged adults in the survivorship setting could be quickly and inexpensively performed using self-reported and easily measured metrics. Full article

Background: Almost half of all patients with non-small-cell lung cancer (nsclc) present with stage iv disease. The objective of the present study was to characterize treatment patterns and survival outcomes in patients with advanced nsclc. Methods: We conducted a longitudinal population-level study in patients diagnosed with stage iv nsclc in Ontario between 1 April 2010 and 31 March 2015, with follow-up to 31 March 2017 for overall survival and treatment sequence. Patients were stratified as nonsquamous or squamous histology. A sub-analysis was conducted for patients with nonsquamous histology who received targeted therapies, on the assumption that their tumours were EGFR mutation–positive (EGFRm+). Treatment patterns were determined, and survival was calculated from date of diagnosis to death or censoring. Results: Of 24,729 nsclc cases identified, stage iv disease was diagnosed in 49.2%, histology was nonsquamous in 10,103, and EGFRm+ was assumed in 508. Median patient age ranged from 69 to 72 years for the three cohorts. For patients with nonsquamous histology, palliative radiotherapy was the most frequently used first-line treatment (44.4%), followed by no treatment (26.7%) and chemotherapy (14.9%). In the EGFRm+ cohort, 75.6% received gefitinib as first- or second-line therapy, and almost half (47.4%) the 473 patients with squamous histology treated with first-line chemotherapy received cisplatin or carboplatin with gemcitabine. Median overall survival in the nonsquamous and squamous cohorts was 4.9 and 4.6 months respectively; it was 17.6 months for patients who were EGFRm+. Conclusions: Survival of patients with stage iv nsclc remains poor, with the exception of patients who are EGFRm+. Only 14.9% of patients received first-line chemotherapy; the mainstay of treatment was palliative radiotherapy. Full article

Background: The management of unresectable stage iii non-small-cell lung cancer (NSCLC) is complex and best determined through multidisciplinary consultation. A longitudinal, population-level study was carried out to describe the management approach and outcomes of treatment in the real-world setting in Ontario. Methods: Individuals diagnosed with nsclc between 1 April 2010 and 31 March 2015 were identified in the Ontario Cancer Registry. Unresectable disease was defined as no surgery reported within 3 months of diagnosis. Initial treatments included radiotherapy (RT, curative or palliative), chemotherapy, targeted therapy, and chemoradiation [CRT, concurrent (cCRT) or sequential (sCRT)]. Survival was calculated from diagnosis with stage III disease to death or last follow-up. Results: Of the 24,729 individuals diagnosed with nsclc, 5243 (21.2%) had stage iii disease, with most of the latter group (4542, 86.6%) having unresectable disease. Median age was 70 years, and 54.2% were men. The frequency of first-line treatment was cCRT, 22.1%; palliative rt, 21.0%; curative rt, 19.6%; no treatment, 19.6%; chemotherapy alone, 11.6%; sCRT, 5.4%; and targeted therapy, 0.7%. Median overall survival (mOS) was 14.2 months [95% confidence interval (CI): 13.6 months to 14.7 months], with the longest survival observed in patients who received targeted therapy (mOS: 34.7 months; 95% CI: 21.4 months to 51.2 months), and the poorest, in those receiving no cancer treatment (mOS: 5.9 months; 95% CI: 5.0 months to 6.4 months). The mOS in patients receiving cCRT was 23.6 months (95% CI: 21.4 months to 25.6 months). Conclusions: Guideline-recommended cCRT is undertaken in only a small proportion of patients with unresectable NSCLC in Ontario. The reasons for low uptake of that recommendation are only partly understood. Full article

Background: Humour has long been considered an important coping tool for patients with cancer, but published quantitative data about its significance are limited. The purpose of our study was to survey patients with cancer undergoing radiotherapy regarding their opinions about the use of humour in their care. Methods: An anonymous 35-item questionnaire evaluating the patient experience, including the value of humour, was developed by an interdisciplinary team of health care providers (HCPS) working within the Radiation Medicine program. This anonymous, voluntary, paper-based survey for self-completion required approximately 10 minutes to finish and was administered during the fall of 2018 and the spring of 2019. Results: For the 199 patients who completed the survey [108 women, 89 men (2 respondents did not specify)], median age was 68 years. That group represents approximately 30%–35% of the patients on treatment during the study period. Almost all respondents (86%) indicated that, during their visits to the cancer centre, it was “somewhat important” or “very important” for health care providers (HCPS) to use appropriate humour, and 61% of respondents indicated using humour “frequently” or “always” when dealing with their individual cancers. Most respondents (79%) said that humour decreased anxiety, and 86% indicated that laughing was considered “somewhat important” or “very important.” Approximately 4% of respondents even listed “sense of humour” as being the most important quality that they looked for in their interactions with their HCPS. Conclusions: Cancer patients undergoing radiotherapy clearly view humour as being important for coping and dealing with their disease, and oncology HCPS should routinely consider incorporating the use of appropriate humour into the care that they provide. Full article

Combined immune checkpoint blockade with nivolumab and ipilimumab is standard therapy for the treatment of patients with previously untreated advanced renal cell carcinoma who are at intermediate or poor risk. However, data about the safety and efficacy of combined immune checkpoint blockade with nivolumab and ipilimumab in patients on hemodialysis are limited. Renal function has no known clinically important effects on the pharmacokinetics and clearance of nivolumab and ipilimumab. Further, most immune-related adverse events in patients on hemodialysis are thought to be manageable with the same treatments applied in patients with normal renal function. We present a case of advanced clear-cell renal cell carcinoma in a patient on hemodialysis who received combined immune checkpoint blockade with nivolumab and ipilimumab and who showed no evident signs of immune-related adverse events. Here, we confirm the safety and efficacy of combined immune checkpoint blockade with nivolumab and ipilimumab in a patient on hemodialysis. Full article

Bone metastases are a significant source of morbidity and mortality for patients with breast and prostate cancer. In this review, we discuss key practical themes regarding the use of bone-targeted agents (btas) such as bisphosphonates and denosumab for managing bony metastatic disease. The btas both delay the onset and reduce the incidence of skeletal-related events (sres), defined as any or all of a need for radiation therapy or surgery to bone, pathologic fracture, spinal cord compression, or hypercalcemia of malignancy. They have more modest benefits for pain and other quality-of-life measures. Regardless of the benefits of btas, it should always be remembered that the palliative management of metastatic bone disease is multimodal and multidisciplinary. The collaboration of all disciplines is essential for optimal patient care. Special consideration is given to these key questions: (1) What are btas, and what is their efficacy? (2) What are their common toxicities? (3) When should they be initiated? (4) How do we choose the appropriate bta? (5) What is the appropriate dose, schedule, and duration of btas? Full article

Background: Pancreatic neuroendocrine tumours (pnets) often present as advanced disease. The optimal sequence of therapy is unknown. Methods: Sequential patients with advanced pnets referred to BC Cancer between 2000 and 2013 who received 1 or more treatment modalities were reviewed, and treatment patterns, progression-free survival (PFS), and overall survival (OS) were characterized. Systemic treatments included chemotherapy, small-molecule therapy, and peptide receptor radionuclide therapy. Results: In 66 cases of advanced pNETs, median patient age was 61.2 years (25%–75% interquartile range: 50.8–66.2 years), and men constituted 47% of the group. First-line therapies were surgery (36%), chemotherapy (33%), and somatostatin analogues (32%). Compared with first-line systemic therapy, surgery in the first line was associated with increased PFS and OS (20.6 months vs. 6.3 months and 100.3 months vs. 30.5 months respectively, p < 0.05). In 42 patients (64%) who received more than 1 line of therapy, no difference in os or pfs between second-line therapies was observed. Conclusions: Our results confirm the primary role of surgery for advanced pNETs. New systemic treatments will further increase options. Full article

Background: The combination of nivolumab and ipilimumab is approved in several jurisdictions (United States, European Union, Canada) for the first-line treatment of patients with advanced melanoma. CheckMate 218 is a North American expanded-access program (EAP) of nivolumab plus ipilimumab in patients with advanced melanoma. Here, we report safety and survival outcomes for the Canadian cohort in the eap. Methods: Eligible patients were those 18 years of age or older with unresectable stage III or IV melanoma, an Eastern Cooperative Oncology Group performance status of 0 or 1, and no prior anti–PD-1 or anti–CTLA-4 therapy. Patients were treated with nivolumab 1 mg/kg and ipilimumab 3 mg/kg every 3 weeks for 4 cycles (induction phase); they then continued with nivolumab 3 mg/kg every 2 weeks (maintenance phase) until progression, unacceptable toxicity, or a maximum of 48 weeks, whichever occurred first. Safety and overall survival (OS) data were collected. Results: Of 194 patients enrolled, 174 were treated, and 51% continued on nivolumab maintenance. Median follow-up was 12.9 months. All-grade and grades 3–4 treatment-related adverse events were reported in 98% and 60% of patients respectively and led to treatment discontinuation in 40% and 28% of patients. Two treatment-related deaths were reported. The 12- and 18-month OS rates were 80% [95% confidence interval (CI): 73% to 86%] and 76% (95% CI: 67% to 82%) respectively. Conclusions: In this Canadian population, nivolumab plus ipilimumab demonstrated a safety profile and survival outcomes consistent with phase II and III clinical trial data. Full article

Background: Venous thromboembolism (VTE) in malignancy is associated with poor outcomes. We conducted a retrospective review of VTE in patients with endometrial cancer to characterize the VTE incidence, identify factors that contribute to VTE risk, and compare survival outcomes in patients with and without VTE. Methods: A retrospective chart review identified 422 eligible patients who underwent surgery for endometrial cancer (1 January 2014 to 31 July 2016). The primary outcome was VTE. Binary logistic regression identified risk factors for VTE; significant risk factors were included in a multivariate analysis. Kaplan–Meier estimates are reported, and log rank tests were used to compare the Kaplan–Meier curves. Risk-adjusted estimates for overall survival based on VTE were determined using a multivariate Cox proportional hazards model. Results: The incidence of VTE was 6.16% overall and 0.7% within 60 days postoperatively. Non-endometrioid histology, stages 3 and 4 disease, laparotomy, and age (p < 0.1) were identified as factors associated with VTE and were included in a multivariate analysis. The overall death rate in patients with VTE was 42% (9% without VTE): hazard ratio, 5.63; 95% confidence interval, 2.86 to 11.08; p < 0.0001. Adjusting for age, stage of disease, and histology, risk of death remained significant for patients with a VTE: hazard ratio, 2.20; 95% confidence interval, 1.09 to 4.42; p = 0.0271. Conclusions: A method to identify patients with endometrial cancer who are at high risk for VTE is important, given the implications of VTE for patient outcomes and the frequency of endometrial cancer diagnoses. Factors identified in our study might assist in the recognition of such patients. Full article

Background: Despite level 1 evidence demonstrating the equivalence of single-fraction radiotherapy (SFRT) and multiple-fraction radiotherapy (MFRT) for the palliation of painful bone metastases, SFRT remains underused. In 2015, to encourage the sustainable use of palliative radiation oncology resources, CancerCare Manitoba disseminated, to each radiation oncologist in Manitoba, guidelines from Choosing Wisely Canada (CWC) that recommend SFRT. We assessed whether dissemination of the guidelines influenced SFRT use in Manitoba in 2016, and we identified factors associated with MFRT. Methods: All patients treated with palliative radiotherapy for bone metastasis in Manitoba from 1 January 2016 to 31 December 2016 were identified from the provincial radiotherapy database. Patient, treatment, and disease characteristics were extracted from the electronic medical record and tabulated by fractionation schedule. Univariable and multivariable logistic regression analyses were performed to identify risk factors associated with MFRT. Results: In 2016, 807 patients (mean age: 70 years; range: 35–96 years) received palliative radiotherapy for bone metastasis, with 69% of the patients having uncomplicated bone metastasis. The most common primary malignancies were prostate (27.1%), lung (20.6%), and breast cancer (15.9%). In 62% of cases, MFRT was used—a proportion that was unchanged from 2015. On multivariable analysis, a gastrointestinal [odds ratio (OR): 5.3] or lung primary (OR: 3.3), complicated bone metastasis (OR: 4.3), and treatment at a subsidiary site (or: 4.4) increased the odds of MFRT use. Conclusions: Dissemination of cwc recommendations alone did not increase SFRT use by radiation oncologists in 2016. A more comprehensive knowledge translation effort is therefore warranted and is now underway to encourage increased uptake of SFRT in Manitoba. Full article

Background: Radiation-induced chest wall pain (CWP) and rib fracture (RF) are late adverse effects after stereotactic body radiation therapy (SBRT) for stage i non-small-cell lung cancer (NSCLC); however, the literature about their incidence and risk factors shows variability. We performed a systematic review to determine the pooled incidence of CWP and RF in the relevant population. Methods: A literature search using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines considered English publications in MEDLINE and EMBASE from January 1996 to August 2017. Abstracts were screened, followed by full-text review and data extraction. Results: The database searches identified 547 records. Twenty-eight publications comprising 3892 patients met the inclusion criteria. Median reported ages and follow-up durations fell into the ranges 67–82 years and 12–84 months. Prescriptions fell into the range of 40–70 Gy in 3–10 fractions. Despite study heterogeneity, the pooled incidences of CWP and RF were estimated to be 8.94% and 5.27% respectively. Nineteen studies reported cwp grade: 58 of 308 patients (18.8%) experienced grades 3–4 CWP (no grade 5 events reported). Thirteen studies reported RF grade: grades 3–4 RF were observed in 9 of 113 patients (7.96%). A high chest wall V30 was an important predictor of CWP and RF. Conclusions: In patients with stage i nsclc, rates of CWP and RF after SBRT are low; however, tumour location, accurate toxicity reporting, and dose–fractionation schemes might alter those rates. Prospective correlation with dosimetry and quality of life assessment will further improve the understanding of CWP and RF after sbrt. Full article