Radiation-Induced Heart Disease

Cancer incidence and survivorship have had a rising tendency over the last two decades due to better treatment modalities. One of these is radiation therapy (RT), which is used in 20–55% of cancer patients, and its basic principle consists of inhibiting proliferation or inducing apoptosis of cancer cells. Classically, photon beam RT has been the mainstay therapy for these patients, but, in the last decade, proton beam has been introduced as a new option. This newer method focuses more on the tumor and affects less of the surrounding normal tissue, i.e., the heart. Radiation to the heart is a common complication of RT, especially in patients with lymphoma, breast, lung, and esophageal cancer. The pathophysiology is due to changes in the microvascular and macrovascular milieu that can promote accelerated atherosclerosis and/or induce fibrosis of the myocardium, pericardium, and valves. These complications occur days, weeks, or years after RT and the risk factors associated are high radiation doses (>30 Gy), concomitant chemotherapy (primarily anthracyclines), age, history of heart disease, and the presence of cardiovascular risk factors. The understanding of these mechanisms and risk factors by physicians can lead to a tailored assessment and monitorization of these patients with the objective of early detection or prevention of radiation-induced heart disease. Echocardiography is a noninvasive method which provides a comprehensive evaluation of the pericardium, valves, myocardium, and coronaries, making it the first imaging tool in most cases; however, other modalities, such as computed tomography, nuclear medicine, or cardiac magnetic resonance, can provide additional value.

Vaginal cancer treated with curative radiotherapy with or without concomitant chemotherapy: oncologic outcomes and prognostic factors

Background: Vaginal cancer is a rare disease for which prospective randomized trials do not exist. We aimed to assess survival outcomes, patterns of recurrence, prognostic factors, and toxicity in the curative treatment using image-guided radiotherapy (RT). Methods: In this retrospective review, we identified 53 patients who were treated at a single center with external beam radiotherapy and brachytherapy with or without concomitant chemotherapy from 2000 to 2021. Results: With a median follow-up of 64.5 months, the Kaplan-Meier 2-, 5-, and 7-year overall survival (OS) was found to be 74.8%, 62.8%, and 58.9%, respectively. Local and distant control were 67.8%, 65.0%, and 65.0% and 74.4%, 62.6%, and 62.6% at 2, 5, and 7 years, respectively. In univariate Cox proportional hazards ratio analysis, OS was significantly correlated to FIGO stage (hazard ratio [HR] 1.78, p = 0.042), postoperative RT (HR 0.41, p = 0.044), and concomitant chemotherapy (HR 0.31, p = 0.009). Local control rates were superior when an equivalent dose in 2-Gy fractions (EQD2) of ⩾65 Gy was delivered (HR 0.216, p = 0.028) and with the use of concurrent chemotherapy (HR 0.248, p = 0.011). Not surprisingly, local control was inferior for patients with a higher TNM stage (HR 3.303, p = 0.027). Minimal toxicity was observed with no patients having documentation of high-grade toxicity (CTCAE grade 3+). Conclusion: In treatment of vaginal cancer, high-dose RT in combination with brachytherapy is well tolerated and results in effective local control rates, which significantly improve with an EQD2(α/β=10) ⩾65 Gy. Multivariate analyses revealed concomitant chemotherapy was a positive prognostic factor for overall and progression-free survival.

Multifocal high-grade glioma radiotherapy safety and efficacy

Background Multifocal manifestation of high-grade glioma is a rare disease with very unfavourable prognosis. The pathogenesis of multifocal glioma and pathophysiological differences to unifocal glioma are not fully understood. The optimal treatment of patients suffering from multifocal high-grade glioma is not defined in the current guidelines, therefore individual case series may be helpful as guidance for clinical decision-making. Methods Patients with multifocal high-grade glioma treated with conventionally fractionated radiation therapy (RT) in our institution with or without concomitant chemotherapy between April 2011 and April 2019 were retrospectively analysed. Multifocality was neuroradiologically assessed and defined as at least two independent contrast-enhancing foci in the MRI T1 contrast-enhanced sequence. IDH mutational status and MGMT methylation status were assessed from histopathology records. GTV, PTV as well as the V30Gy, V45Gy and D2% volumes of the brain were analysed. Overall and progression-free survival were calculated from the diagnosis until death and from start of radiation therapy until diagnosis of progression of disease in MRI for all patients. Results 20 multifocal glioma cases (18 IDH wild-type glioblastoma cases, one diffuse astrocytic glioma, IDH wild-type case with molecular features of glioblastoma and one anaplastic astrocytoma, IDH wild-type case) were included into the analysis. Resection was performed in two cases and stereotactic biopsy only in 18 cases before the start of radiation therapy. At the start of radiation therapy patients were 61 years old in median (range 42–84 years). Histopathological examination showed IDH wild-type in all cases and MGMT promotor methylation in 11 cases (55%). Prescription schedules were 60 Gy (2 Gy × 30), 59.4 Gy (1.8 Gy × 33), 55 Gy (2.2 Gy × 25) and 50 Gy (2.5 Gy × 20) in 15, three, one and one cases, respectively. Concomitant temozolomide chemotherapy was applied in 16 cases, combined temozolomide/lomustine chemotherapy was applied in one case and concomitant bevacizumab therapy in one case. Median number of GTVs was three. Median volume of the sum of the GTVs was 26 cm3. Median volume of the PTV was 425.7 cm3 and median PTV to brain ratio 32.8 percent. Median D2% of the brain was 61.5 Gy (range 51.2–62.7) and median V30Gy and V45 of the brain were 59.9 percent (range 33–79.7) and 40.7 percent (range 14.9–64.1), respectively. Median survival was eight months (95% KI 3.6–12.4 months) and median progression free survival after initiation of RT five months (95% CI 2.8–7.2 months). Grade 2 toxicities were detected in eight cases and grade 3 toxicities in four cases consisting of increasing edema in three cases and one new-onset seizure. One grade 4 toxicity was detected, which was febrile neutropenia related to concomitant chemotherapy. Conclusion Conventionally fractionated RT with concomitant chemotherapy could safely be applied in multifocal high-grade glioma in this case series despite large irradiation treatment fields.

Clinical predictive markers of response to immune checkpoint inhibitor therapy in advanced non-small cell lung cancer.

e21044 Background: Overweight and obesity have been associated with improved overall survival (OS) and progression-free survival (PFS) in patients treated with immune checkpoint inhibitors (ICI). EPSILoN score (EPSILoN), comprised of five clinical variables (smoking, Eastern Cooperative Oncology Group performance status, liver metastases, lactate dehydrogenase (LDH), and neutrophil-lymphocyte ratio), is a known predictive marker of response to ICI. This study aims to validate body mass index (BMI) and EPSILoN as predictive markers of response in frontline treatment of advanced non-small cell lung cancer (NSCLC) with ICI with or without concomitant chemotherapy. Methods: Patients with advanced NSCLC who received frontline ICI were identified using the electronic medical record. PFS and OS were retrospectively evaluated and stratified based on baseline BMI and EPSILoN. Due to lack of routine LDH testing, a modified EPSILoN (mEPSILoN) was used. For statistical analysis, log-rank tests were used to compare PFS and OS between groups, and Kaplan-Meier survival curves were used to report PFS and OS. Results: Thirty-six normal weight (NW) and 25 overweight and obese (OWO) patients were studied. Median PFS (mPFS) for OWO vs NW patients was 8.90 months vs 5.53 months (HR 0.54; 95% CI, 0.30-0.96; p = 0.04). mPFS at 12 months was 45% for OWO patients vs 23% for NW patients. Of the patients with PD-L1 ≥ 50%, 14 patients were NW and 11 patients were OWO. Among patients with PD-L1 ≥ 50%, mPFS for OWO was not reached (NR) vs 6.73 months in NW patients (HR 0.23; 95% CI, 0.09-0.60; p = 0.003), and the percent of patients that were PF at 12 months was 71% vs 15%. Of 56 patients with a calculable mEPSILoN, 29 patients had baseline mEPSILoN 1 and 27 patients had mEPSILoN 2-3. Median OS for patients with mEPSILoN 1 vs 2-3 was NR vs 11.13 months (HR 0.32; 95% CI, 0.14-0.76; p = 0.01) and 78% vs 49% survived at 12 months. Conclusions: OWO and lower mEPSILoN were associated with longer PFS and OS, respectively, in patients with advanced NSCLC who were treated with frontline ICI with or without concomitant chemotherapy, regardless of PD-L1 expression. These findings are consistent with recent studies that have reported these parameters as predictive markers of response in patients with NSCLC. However, this is the first study to our knowledge to evaluate these markers in frontline ICI treatment with or without chemotherapy.[Table: see text]

Salvage radiotherapy for postoperative locoregional failure in esophageal cancer: a systematic review and meta-analysis

Summary Locoregional recurrences following surgery for esophageal cancers represent a significant clinical problem with no standard recommendations for management. We conducted this systematic review and meta-analysis with the objective of studying safety and efficacy of salvage radiotherapy in this setting. All prospective and retrospective cohort studies, which studied patients who developed locoregional recurrence following initial radical surgery for esophageal cancer and subsequently received salvage radiation therapy (RT)/chemoradiation with all relevant information regarding survival outcome and toxicity available, were included. The quality of eligible individual studies was assessed using the Newcastle-Ottawa Scale score for risk of bias. R package MetaSurv was used to obtain a summary survival curve from survival probabilities and numbers of at-risk patients collected at various time points and to test the overall heterogeneity using the I2 statistic. Thirty studies (27 retrospective, 3 prospective) published from 1995 to 2020 with 1553 patients were included. The median interval between surgery and disease recurrence was 12.5 months. The median radiation dose used was 60 Gy and 57% received concurrent chemotherapy. The overall incidence of acute grade 3/4 mucositis and dermatitis were 8 and 4%, respectively; grade 3/4 acute pneumonitis was reported in 5%. The overall median follow-up of all studies included was 27 months. The 1-, 2- and 3-year overall survival (OS) probabilities were 67.9, 35.9 and 30.6%, respectively. Factors which predicted better survival on multivariate analysis were good PS, lower group stage, node negativity at index surgery, longer disease-free interval, nodal recurrence (as compared to anastomotic site recurrence), smaller disease volume, single site of recurrence, RT dose >50 Gy, conformal RT, use of concomitant chemotherapy and good radiological response after radiotherapy. Salvage radiotherapy with or without concomitant chemotherapy for locoregional recurrences after surgery for esophageal cancer is safe and effective. Modern radiotherapy techniques may improve outcomes and reduce treatment-related morbidity.

Anal cancer - impact of interstitial brachytherapy

We evaluated a total of 115 patients diagnosed with anal cancer, who were treated at our clinic from 1995 to 2012. Their average age was 61 years, most often were diagnosed in stages II and III, in most cases it was a squamous cell carcinoma located in the anal canal. The mean follow-up was 83 months (minimum 1 month and maximum 240 months). We combined external radiotherapy with boost of brachytherapy or boost of external radiotherapy and possibly a combination of both boosts. Half of the patients received concomitant chemotherapy. We specifically evaluated local tumor regression, overall survival and the impact to therapeutic effect of the chosen irradiation technique. Complete regression was achieved in 92 patients, partial regression in 21 patients. Overall survival, regardless of stage, was 80% 3-year, 74% 5-year and 67% 10-year. The age of patients, the size of their own primary tumor and the therapeutic method used had a statistically significant effect on survival - especially the importance of brachytherapy was irreplaceable.