Explore association of genes in PDL1/PD1 pathway to radiotherapy survival benefit based on interaction model strategy.

PURPOSE: To explore the association of genes in "PD-L1 expression and PD-1 check point pathway in cancer" to radiotherapy survival benefit. METHODS AND MATERIALS: Gene expression data and clinical information of cancers were downloaded from TCGA. Radiotherapy survival benefit was defined based on interaction model. Fast backward multivariate Cox regression was performed using stacking multiple interpolation data to identify radio-sensitive (RS) genes. RESULTS: Among the 73 genes in PD-L1/PD-1 pathway, we identified 24 RS genes in BRCA data set, 25 RS genes in STAD data set and 20 RS genes in HNSC data set, with some crossover genes. Theoretically, there are two types of RS genes. The expression level of Type I RS genes did not affect patients' overall survival (OS), but when receiving radiotherapy, patients with different expression level of Type I RS genes had varied survival benefit. Oppositely, Type II RS genes affected patients' OS. And when receiving radiotherapy, those with lower OS could benefit a lot. Type II RS genes in BRCA had strong positive correlation and closely biological interactions. When performing cluster analysis using these related Type II RS genes, patients could be divided into RS group and non-RS group in BRCA and METABRIC data sets. CONCLUSIONS: Our study explored potential radio-sensitive biomarkers of several main cancer types in an important tumor immune checkpoint pathway and revealed a strong association between this pathway and radiotherapy survival benefit. New types of RS genes could be identified based on expanded definition to RS genes.

Updated Outcomes of Split Course Radiotherapy in Elderly or Infirm Patients With Advanced Cancers of the Head and Neck.

BACKGROUND/AIM: Head and neck cancers are often treated with extended courses of radiotherapy (RT), which may prove excessively toxic for frail patients. Split course RT (SCRT) delivers two courses of RT separated by 4-6 weeks, personalizing treatment intensity based on response. In this study, we present our updated experience using this technique. PATIENTS AND METHODS: From a single institution database, we identified patients considered for SCRT. For patients undergoing a second course of RT, cumulative incidence of locoregional recurrence (LRR) and overall survival (OS) are reported. RESULTS: A total of 98 patients were included, of whom seventy-five percent underwent a second course of RT. The most common fractionation was 30 Gy in 10 fractions for each course, with a median cumulative dose of 60 Gy. In those undergoing a second course of RT, median OS was 9.7 months and cumulative incidence of LRR at 6, 12, and 24 months was 17.0%, 23.1%, and 29.4%, respectively. CONCLUSION: SCRT offers an attractive treatment paradigm to personalize radiation intensity based on patient tolerance, while maintaining reasonable safety and efficacy in those unfit for standard full course RT.

Outcomes in primary cutaneous diffuse large B-cell lymphoma, leg type.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT) is a rare, aggressive lymphoma characterized by skin involvement predominantly in the lower extremities. Immunochemotherapy with or without involved-site radiation therapy (ISRT) is considered standard front-line therapy. Over-expression of PD-L1/PD-L2 is seen in a high proportion of PCDLBCL, LT cases, but efficacy of immune checkpoint inhibitors (ICI) in relapsed/refractory, PCDLBCL, LT has not been thoroughly studied. We conducted a retrospective cohort study of patients diagnosed with PCDLBCL, LT seen at Mayo Clinic from 1 January 2000 to 31 December 2020. Using the Kaplan-Meier method, we calculated progression-free survival, duration of response, and overall survival in patients who received front-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with and without ISRT, and salvage ICI therapy for relapsed/refractory disease. A total of 28 patients with PCDLBCL, LT were identified. The median PFS in patients treated with R-CHOP plus ISRT was 58 months (95% CI: 18-112) compared to 14 months (95% CI: 5-not reached; p = 0.04) in those treated with R-CHOP without ISRT. The median PFS from salvage ICI therapy was 10 months (95% CI: 4-not reached), and median DOR from salvage ICI therapy was 23 months [95% CI: 4-26]. R-CHOP with ISRT had a significantly longer median PFS compared to R-CHOP without ISRT as front-line therapy for PCDLBCL, LT. ICIs may have a role in treating relapsed/refractory disease as reasonable activity in heavily pre-treated patients was observed in this study.

Predictive value of transcriptional expression of Krüppel-like factor-6 (KLF6) in head and neck carcinoma patients treated with radiotherapy.

PURPOSE: To analyse the relationship between the transcriptional expression of Krüppel-like factor-6 (KLF6) and local response to treatment with radiotherapy in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: We determined the transcriptional expression of KLF6 in tumour biopsies obtained before treatment with radiotherapy in 83 HNSCC patients. The KLF6 expression was categorized according to the local control of the disease with a recursive partitioning analysis. RESULTS: During the follow-up period, 27 patients (32.5%) had a local recurrence of the tumour. Patients with local recurrence had significantly higher levels of KLF6 expression than patients in which radiotherapy achieved local control of the disease (P = 0.029). Five-year local recurrence-free survival for patients with a high transcriptional expression of KLF6 (n = 46) was 51.1% (95% CI 36.4-66.2%), and for patients with low expression it was 85.6% (95% CI 73.9-97.3%) (P = 0.0001). The results of a multivariate analysis showed that patients with a high KLF6 expression had a 3.8 times higher risk of local recurrence after treatment with radiotherapy (95% CI 1.4-10.5, P = 0.008). CONCLUSION: Transcriptional expression of KLF6 was significantly related to local control in HNSCC patients treated with radiotherapy. Patients with high levels of KLF6 expression had a significantly higher risk of local recurrence after treatment.

Lumpectomy followed by radiation improves survival in HER2 positive and triple-negative breast cancer with high tumor-infiltrating lymphocytes compared to mastectomy alone.

OBJECTIVE: The goal was to compare the 5-year DFS and 5-year OS in patients with early-stage human epidermal growth factor receptor 2 breast cancer (HER2+ BC) and triple-negative breast cancer (TNBC) in relation to the amount of stromal tumor-infiltrating lymphocytes (TILs) after locoregional management by either mastectomy without radiation or lumpectomy and whole-breast radiotherapy (RT). METHODS: This was a retrospective review of HER2+ BC and TNBC patients' charts and histopathology slides with clinical stage of T1-T2 N0 who presented at our facility between January 2009 and December 2019. Locoregional treatment included either mastectomy without RT (M) or lumpectomy with RT (L+R). TILs were assessed by three pathologists using the guidelines of the 2014 TILs working group. A competing risk model and Kaplan-Meier analysis were used to analyze correlations between TILs levels and clinical outcome. RESULTS: We reviewed 211 patients' charts. Of them, 190 proceeded to the final analysis. Patients were split into groups of "low TILs" and "high TILs" based on a 50% TILs cut-off. Of them 26% had high TILs, 48% received RT, 97% received chemotherapy, all HER2+ BC patients received HER2-directed therapy and all HER2+ BC that were also hormone receptor positive (HR+) received endocrine therapy (ET). In patient with low TILs, L+R did not improve outcomes compared to M. Moreover, patients with high TILs had a significant improvement of their DFS and OS with L+R when compared to M. CONCLUSION: The results of our study reflect that a selected group of HER2+ BC and TNBC with elevated TILs, L+R is associated with improvement of 5-year DFS and 5-year OS.

Pediatric Pleomorphic Xanthoastrocytoma: A National Database Inquiry on Current Treatment Approaches in the United States.

BACKGROUND: Pleomorphic xanthoastrocytomas (PXAs) account for <1% of primary brain tumors, occurring predominantly in children and young adults. Surgical resection serves as the primary treatment for PXAs, while radiotherapy (RT) and chemotherapy protocols remain poorly defined. AIM: This study aims to determine current care patterns utilized for pediatric patients (≤ 18 years) diagnosed with PXAs and their effect on overall survival. METHODS: The United States National Cancer Database (NCDB) was queried between 2004 and 2015 for pediatric patients (≤18 years) diagnosed with PXAs. RESULTS: From the 224 qualifying patients, most patients proceeded with surgery only (78.1%), while 11.6% of patients received both adjuvant RT and chemotherapy. In the 2010-2015 cohort, patients with subtotal resection were associated with poorer prognosis than those with gross-total resection (hazard ratio = 17.44, 95% confidence interval = 2.10-144.90, p < .001). RT and chemotherapy recipients were similarly associated with poorer survival than those treated with surgery only, with p-values of <.001 and respective hazard ratios of 3.82 (95% confidence interval = 1.85-7.90) and 6.68 (95% confidence interval = 3.21-13.89). The key factors impacting the probability of RT delivery involved WHO grade (p < .001) and chemotherapy administration (p < .001). However, WHO grade alone did not significantly impact survival (p-value = .088). CONCLUSION: Maximally safe resection is the current treatment goal for patients with PXAs. RT and chemotherapy are poorly utilized but had a greater role in managing more aggressive cases of PXAs. Additional research focusing on the impact of adjuvant therapies on tumor progression is needed to better guide treatment decisions.

High-dose versus standard-dose twice-daily thoracic radiotherapy for patients with limited stage small-cell lung cancer: an open-label, randomised, phase 2 trial.

BACKGROUND: Concurrent chemoradiotherapy is standard treatment for limited stage small-cell lung cancer (SCLC). Twice-daily thoracic radiotherapy of 45 Gy in 30 fractions is considered to be the most effective schedule. The aim of this study was to investigate whether high-dose, twice-daily thoracic radiotherapy of 60 Gy in 40 fractions improves survival. METHODS: This open-label, randomised, phase 2 trial was done at 22 public hospitals in Norway, Denmark, and Sweden. Patients aged 18 years and older with treatment-naive confirmed limited stage SCLC, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and measurable disease according to the Response Evaluation Criteria in Solid Tumors version 1.1 were eligible. All participants received four courses of intravenous cisplatin 75 mg/m2 or carboplatin (area under the curve 5-6 mg/mL × min, Calvert's formula) on day 1 and intravenous etoposide 100 mg/m2 on days 1-3 every 3 weeks. Participants were randomly assigned (1:1) in permuted blocks (sized between 4 and 10) stratifying for ECOG performance status, disease stage, and presence of pleural effusion to receive thoracic radiotherapy of 45 Gy in 30 fractions or 60 Gy in 40 fractions to the primary lung tumour and PET-CT positive lymph node metastases starting 20-28 days after the first chemotherapy course. Patients in both groups received two fractions per day, ten fractions per week. Responders were offered prophylactic cranial irradiation of 25-30 Gy. The primary endpoint, 2-year overall survival, was assessed after all patients had been followed up for a minimum of 2 years. All randomly assigned patients were included in the efficacy analyses, patients commencing thoracic radiotherapy were included in the safety analyses. Follow-up is ongoing. This trial is registered at ClinicalTrials.gov, NCT02041845. FINDINGS: Between July 8, 2014, and June 6, 2018, 176 patients were enrolled, 170 of whom were randomly assigned to 60 Gy (n=89) or 45 Gy (n=81). Median follow-up for the primary analysis was 49 months (IQR 38-56). At 2 years, 66 (74·2% [95% CI 63·8-82·9]) patients in the 60 Gy group were alive, compared with 39 (48·1% [36·9-59·5]) patients in the 45 Gy group (odds ratio 3·09 [95% CI 1·62-5·89]; p=0·0005). The most common grade 3-4 adverse events were neutropenia (72 [81%] of 89 patients in the 60 Gy group vs 62 [81%] of 77 patients in the 45 Gy group), neutropenic infections (24 [27%] vs 30 [39%]), thrombocytopenia (21 [24%] vs 19 [25%]), anaemia (14 [16%] vs 15 [20%]), and oesophagitis (19 [21%] vs 14 [18%]). There were 55 serious adverse events in 38 patients in the 60 Gy group and 56 serious adverse events in 44 patients in the 45 Gy group. There were three treatment-related deaths in each group (one neutropenic fever, one aortic dissection, and one pneumonitis in the 60 Gy group; one thrombocytic bleeding, one cerebral infarction, and one myocardial infarction in the 45 Gy group). INTERPRETATION: The higher radiotherapy dose of 60 Gy resulted in a substantial survival improvement compared with 45 Gy, without increased toxicity, suggesting that twice-daily thoracic radiotherapy of 60 Gy is an alternative to existing schedules. FUNDING: The Norwegian Cancer Society, The Liaison Committee for Education, Research and Innovation in Central Norway, the Nordic Cancer Union, and the Norwegian University of Science and Technology.

Impact of family history on oncological outcomes in primary therapy for localized prostate cancer patients: a systematic review and meta-analysis.

BACKGROUND: The influence of family history on oncological outcomes of prostate cancer remains controversial. We conducted a systematic literature review and meta-analysis to investigate the impact of family history of localized prostate cancer on oncological outcomes. METHODS: On May 2020, we systematically searched MEDLINE, the Cochrane library, and Scopus for studies that compared patients who had localized prostate cancer with or without a positive family history of prostate cancer. Our aim was to evaluate the association of family history with biochemical recurrence-free survival, cancer-specific survival, and overall survival by means of a multivariate Cox regression analysis. RESULTS: Eleven studies with 39,716 patients were included in the systematic review, and eight studies with 33,027 patients for the meta-analysis. A positive family history was not associated with worse biochemical recurrence-free survival (pooled HR: 0.96; 95% CI: 0.79-1.17) or cancer-specific survival (pooled HR: 1.1; 95% CI: 0.52-2.35). Subgroup analyses showed no association between positive family history and poor biochemical recurrence-free survival in prostate cancer patients treated with radical prostatectomy (pooled HR: 0.99; 95% CI: 0.76-1.31) or radiation therapy (pooled HR: 0.93; 95% CI: 0.67-1.30). CONCLUSIONS: This meta-analysis indicated that family history of prostate cancer does not increase the risk of biochemical recurrence or cancer-specific mortality in localized prostate cancer patients.

Survival from breast cancer in women with a BRCA2 mutation by treatment.

BACKGROUND: The impact of various breast-cancer treatments on patients with a BRCA2 mutation has not been studied. We sought to estimate the impact of bilateral oophorectomy and other treatments on breast cancer-specific survival among patients with a germline BRCA2 mutation. METHODS: We identified 664 women with stage I-III breast cancer and a BRCA2 mutation by combining five different datasets (retrospective and prospective). Subjects were followed for 7.2 years from diagnosis to death from breast cancer. Tumour characteristics and cancer treatments were patient-reported and derived from medical records. Predictors of survival were determined using Cox proportional hazard models, adjusted for other treatments and for prognostic features. RESULTS: The 10-year breast-cancer survival for ER-positive patients was 78.9% and for ER-negative patients was 82.3% (adjusted HR = 1.23 (95% CI, 0.62-2.45, p = 0.55)). The 10-year breast-cancer survival for women who had a bilateral oophorectomy was 89.1% and for women who did not have an oophorectomy was 59.0% (adjusted HR = 0.45; 95% CI, 0.28-0.72, p = 0.001). The adjusted hazard ratio for chemotherapy was 0.83 (95% CI, 0.65-1.53: p = 0.56). CONCLUSIONS: For women with breast cancer and a germline BRCA2 mutation, positive ER status does not predict superior survival. Oophorectomy is associated with a reduced risk of death from breast cancer and should be considered in the treatment plan.

4 Gy versus 24 Gy radiotherapy for follicular and marginal zone lymphoma (FoRT): long-term follow-up of a multicentre, randomised, phase 3, non-inferiority trial.

BACKGROUND: The optimal radiotherapy dose for indolent non-Hodgkin lymphoma is uncertain. We aimed to compare 24 Gy in 12 fractions (representing the standard of care) with 4 Gy in two fractions (low-dose radiation). METHODS: FoRT (Follicular Radiotherapy Trial) is a randomised, multicentre, phase 3, non-inferiority trial at 43 study centres in the UK. We enrolled patients (aged >18 years) with indolent non-Hodgkin lymphoma who had histological confirmation of follicular lymphoma or marginal zone lymphoma requiring radical or palliative radiotherapy. No limit on performance status was stipulated, and previous chemotherapy or radiotherapy to another site was permitted. Radiotherapy target sites were randomly allocated (1:1) either 24 Gy in 12 fractions or 4 Gy in two fractions using minimisation and stratified by histology, treatment intent, and study centre. Randomisation was centralised through the Cancer Research UK and University College London Cancer Trials Centre. Patients, treating clinicians, and investigators were not masked to random assignments. The primary endpoint was time to local progression in the irradiated volume based on clinical and radiological evaluation and analysed on an intention-to-treat basis. The non-inferiority threshold aimed to exclude the chance that 4 Gy was more than 10% inferior to 24 Gy in terms of local control at 2 years (HR 1·37). Safety (in terms of adverse events) was analysed in patients who received any radiotherapy and who returned an adverse event form. FoRT is registered with ClinicalTrials.gov, NCT00310167, and the ISRCTN Registry, ISRCTN65687530, and this report represents the long-term follow-up. FINDINGS: Between April 7, 2006, and June 8, 2011, 614 target sites in 548 patients were randomly assigned either 24 Gy in 12 fractions (n=299) or 4 Gy in two fractions (n=315). At a median follow-up of 73·8 months (IQR 61·9-88·0), 117 local progression events were recorded, 27 in the 24 Gy group and 90 in the 4 Gy group. The 2-year local progression-free rate was 94·1% (95% CI 90·6-96·4) after 24 Gy and 79·8% (74·8-83·9) after 4 Gy; corresponding rates at 5 years were 89·9% (85·5-93·1) after 24 Gy and 70·4% (64·7-75·4) after 4 Gy (hazard ratio 3·46, 95% CI 2·25-5·33; p<0·0001). The difference at 2 years remains outside the non-inferiority margin of 10% at -13·0% (95% CI -21·7 to -6·9). The most common events at week 12 were alopecia (19 [7%] of 287 sites with 24 Gy vs six [2%] of 301 sites with 4 Gy), dry mouth (11 [4%] vs five [2%]), fatigue (seven [2%] vs five [2%]), mucositis (seven [2%] vs three [1%]), and pain (seven [2%] vs two [1%]). No treatment-related deaths were reported. INTERPRETATION: Our findings at 5 years show that the optimal radiotherapy dose for indolent lymphoma is 24 Gy in 12 fractions when durable local control is the aim of treatment. FUNDING: Cancer Research UK.

Personalised support of brain tumour patients during radiotherapy based on psychological profile and quality of life.

PURPOSE: Psychological distress in primary malignant brain tumour (PMBT) patients is associated with poorer outcomes. Radiotherapy (RT) often induces side effects that significantly influence patients' quality of life (QoL), with potential impact on survival. We evaluated distress, anxiety, depression, and QoL over time to identify patients with difficulties in these areas who required more intense psychological support. METHODS: Psychological questionnaires-Distress Thermometer (DT), Hospital Anxiety and Depression Scale (HADS), and Functional Assessment of Cancer Therapy (FACT-G and FACT-Br)-were completed at the beginning (T0), in the middle (T1), directly after RT (T2), and 3 months after RT (T3). We personalised the psychological support provided for each patient with a minimum of three sessions ('typical' schedule) and a maximum of eight sessions ('intensive' schedule), depending on the patients' psychological profiles, clinical evaluations, and requests. Patients' survival was evaluated in the glioblastoma multiforme (GBM) patients, with an explorative intent. RESULTS: Fifty-nine consecutive PMBT patients receiving post-operative RT were included. For patients who were reported as 'not distressed' at T0, no statistically significant changes were noted. In contrast, patients who were 'distressed' at T0 showed statistically significant improvements in DT, HADS, FACT-G, and FACT-Br scores over time. 'Not distressed' patients required less psychological sessions over the study duration than 'distressed' patients. Interestingly, 'not distressed' GBM patients survived longer than 'distressed' GBM patients. CONCLUSIONS: Increased psychological support improved distress, mood, and QoL for patients identified as 'distressed', whereas psychological well-being was maintained with typical psychological support in patients who were identified as being 'not distressed'. These results encourage a standardisation of psychological support for all RT patients.

Factors affecting survival in glioblastoma patients below and above 65 years of age: A retrospective observational study.

BACKGROUND: The purpose of this study is to identify the differences with respect to survival and prognostic factors in a comparison between radiotherapy-receiving glioblastoma (GBM) patients above and below 65 years of age. METHODS: The results of 157 patients with GBM were analyzed retrospectively. Patients were divided into two groups as those below and above 65 years of age. A comparison was drawn with respect to each group's demographic characteristics, treatment methods, and findings. RESULTS: Out of a total of 157 patients, 53 patients (33.8%) were above 65 years of age. Karnofsky performance status (KPS) was weaker among older patients (P = 0.002). On the other hand, with respect to radiotherapy dose, among older patient group, greater hypofractionation and whole-brain radiotherapy was applied (P = 0.003) compared with younger patients. The survival rates for 1, 2, and 5 years among patients aged <65 years were 63%, 30%, and 3%, respectively, and in patients aged ≥65 years were 43%, 13%, and 0%, respectively. In univariate analyses, a comparison between patients below and above 65 years of age revealed that values higher than 80 KPS (P = 0.002), applying total excision (P < 0.001), receiving concurrent chemotherapy (P = 0.004), receiving conventional radiotherapy (P < 0.001), and adjuvant chemotherapy (P < 0.001) were effective factors on overall survival rates. CONCLUSION: In the patient group above 65 years of age, the patient should be attentively selected before opting for a specific treatment, age alone should not be the sole determinant factor. Rather, by considering the KPS scores, potential aggressive treatment options should also be applied.

Early Mortality after Radical Radiotherapy in Head and Neck Cancer - A Nationwide Analysis from the Danish Head and Neck Cancer Group (DAHANCA) Database.

AIMS: Curative-intent radiotherapy (RT) or chemoradiation (CRT) of squamous cell carcinoma of the head and neck (HNSCC) produces high survival rates, but is associated with substantial toxicity. However, there are no commonly accepted quality metrics for early mortality in radiation oncology. To assess the applicability of early mortality as a clinical quality indicator, this study investigated the temporal distribution, risk factors and trends of 90- and 180-day overall and non-cancer mortality in a nationwide cohort of HNSCC patients treated with RT/CRT. MATERIALS AND METHODS: Information on all HNSCC patients treated with curative-intent RT/CRT in Denmark between 2000 and 2017 was obtained from the national Danish Head and Neck Cancer Group clinical database. Deaths in patients with residual or recurrent disease after RT/CRT were classified as cancer-related. Possible risk factors were investigated using logistic regression analysis. RESULTS: Data from 11 419 patients were extracted. In total, 90- and 180-day mortality risks were 3.1% and 7.1%, respectively. There was a uniform temporal distribution of 180-day mortality. In multivariable analysis, increasing age, stage, performance status, earlier treatment year and hypopharyngeal cancer were significantly associated with an increased risk (P < 0.05). Risk factor estimates were comparable for 90- versus 180-day mortality as well as for overall versus non-cancer mortality. Between 2000 and 2017 there was a significant decrease in 180-day mortality, which was driven by a reduction in cancer-related events. CONCLUSION: The distribution of 180-day overall and non-cancer mortality did not indicate a well-defined early high-risk period. Moreover, risk factor estimates were highly similar across risk periods and groups. Taken together, our findings question the applicability of early mortality as a standard metric for treatment-associated toxicity.

Laser Microsurgery Versus Radiotherapy Versus Open Partial Laryngectomy for T2 Laryngeal Carcinoma: A Systematic Review of Oncological Outcomes.

INTRODUCTION: The aim of the current systematic review is to update the pooled survival outcome of patients with T2 glottic carcinoma treated with either laser surgery (CO2 transoral laser microsurgery [CO2 TOLMS]), radiotherapy (RT), or open partial laryngectomy (OPL). METHODS: A systematic search was performed using the MEDLINE database, Scopus, and Google scholar. The inclusion criteria were studies of patients with T2N0 glottic tumor, treated with either primary CO2 TOLMS, definitive curative RT, or primary OPL, and with reported oncological outcome at 5 years calculated with a Kaplan-Meier or Cox regression method. RESULTS: The results of the current review show that local control (LC) is higher with OPL 94.4%, while there are no differences in LC at 5-year posttreatment for patients treated with RT, compared to those treated with CO2 TOLMS (respectively, 75.6% and 75.4%). Primary treatment with OPL and CO2 TOLMS results in higher laryngeal preservation than primary treatment with RT (respectively 95.8%, 86.9%, and 82.4%). CONCLUSION: First-line treatment with OPL and CO2 TOLMS should be encouraged in selected T2 patients, because it results in higher laryngeal preservation and similar LC compared to primary treatment with RT. The involvement of the anterior commissure in the craniocaudal plane and T2b impaired vocal cord mobility have a poorer prognosis and LC compared to patients with T2a tumors for both CO2 TOLMS and RT.

Relationship between treatment center case volume and survival for localized Ewing sarcoma: The role of radiotherapy timing.

In the treatment of localized Ewing sarcoma (EWS), delays in local therapy are known to adversely impact overall survival (OS). However, the role of treatment center volume in EWS outcomes, and the interaction between center volume and local therapy timing with definitive radiotherapy, remains unknown. Using the National Cancer Database, we demonstrate that treatment at the lowest EWS volume centers is associated with reduced OS, explained partly by higher rates of delayed local therapy. Treatment at the highest volume centers results in improved OS, but appears independent of radiotherapy timing. Future efforts to improve care for EWS patients across treatment centers are imperative.

Consolidative Radiotherapy in Oligometastatic Lung Cancer: Patient Selection With a Prediction Nomogram.

BACKGROUND: Patients with stage IV oligometastatic (≤ 3 sites) non-small-cell lung cancer have a progression-free survival (PFS) and overall survival benefit when all sites of metastatic disease and the primary tumor are treated radically with consolidative radiotherapy (cRT). However, the optimal selection of patients most likely from cRT is yet to be defined. PATIENTS AND METHODS: Patients with metastatic non-small-cell lung cancer treated with definitive radiotherapy to all metastatic sites and primary tumor (2008-2019) were retrospectively identified. Univariable Cox proportional-hazards model was used to compare outcomes with demographic and clinical characteristics. A predictive nomogram model for selection of patients most likely to benefit from cRT was constructed. RESULTS: There were 91 patients identified with a total of 114 metastases treated. Median PFS from the start of cRT was 10.9 months (95% confidence interval [CI], 8.1-16.6), while the median survival time was 37.0 months (95% CI, 31.3-NR). On univariable modeling, patients with squamous histology (hazard ratio, 4.16; 95% CI, 1.99-8.71; P < .001) and those treated with non-stereotactic body radiotherapy hypofractionated therapy (hazard ratio, 5.43; 95% CI, 2.10-14.01; P < .001) had worse overall survival, while patients with targetable mutations (hazard ratio, 0.49; 95% CI, 0.25-0.98; P = .04) had a longer survival. Using a predictive nomogram model, patients with a solitary site of metastasis, targetable mutations, intracranial disease, and metachronous timing of oligometastases had a larger PFS benefit from cRT. CONCLUSION: cRT is associated with favorable outcomes in PFS and overall survival. These results may aid in patient counseling, selection for aggressive local therapy, and stratification in future prospective clinical trials.

Toxicity of internal mammary irradiation in breast cancer. Are concerns still justified in times of modern treatment techniques?

BACKGROUND: The purpose of this study was to estimate the additional risk of side effects attributed to internal mammary node irradiation (IMNI) as part of regional lymph node irradiation (RNI) in breast cancer patients and to compare it with estimated overall survival (OS) benefit from IMNI. MATERIAL AND METHODS: Treatment plans (n = 80) with volumetric modulated arc therapy (VMAT) were calculated for 20 patients (4 plans per patient) with left-sided breast cancer from the prospective GATTUM trial in free breathing (FB) and in deep inspiration breath hold (DIBH). We assessed doses to organs at risk ((OARs) lung, contralateral breast and heart) during RNI with and without additional IMNI. Based on the OAR doses, the additional absolute risks of 10-year cardiac mortality, pneumonitis, and secondary lung and breast cancer were estimated using normal tissue complication probability (NTCP) and risk models assuming different age and risk levels. RESULTS: IMNI notably increased the mean OAR doses. The mean heart dose increased upon IMNI by 0.2-3.4 Gy (median: 1.9 Gy) in FB and 0.0-1.5 Gy (median 0.4 Gy) in DIBH. However, the estimated absolute additional 10-year cardiac mortality caused by IMNI was <0.5% for all patients studied except 70-year-old high risk patients (0.2-2.4% in FB and 0.0-1.1% in DIBH). In comparison to this, the published oncological benefit of IMNI ranges between 3.3% and 4.7%. The estimated additional 10-year risk of secondary cancer of the lung or contralateral breast ranged from 0-1.5% and 0-2.8%, respectively, depending on age and risk levels. IMNI increased the pneumonitis risk in all groups (0-2.2%). CONCLUSION: According to our analyses, the published oncological benefit of IMNI outweighs the estimated risk of cardiac mortality even in case of (e.g., cardiac) risk factors during VMAT. The estimated risk of secondary cancer or pneumonitis attributed to IMNI is low. DIBH reduces the estimated additional risk of IMNI even further and should be strongly considered especially in patients with a high baseline risk.

High Biologically Effective Dose Radiotherapy for Brain Metastases May Improve Survival and Decrease Risk for Local Relapse Among Patients With Small-Cell Lung Cancer: A Propensity-Matching Analysis.

To evaluate whether high biologically effective dose (BED) radiotherapy improves local control and survival outcomes for patients with brain metastases (BMs) from small-cell lung cancer (SCLC) and to determine possible prognostic factors. From January 1998 to June 2018, 250 patients with BM from SCLC were retrospectively analyzed. The Cutoff Finder program was used to classify patients by BED. Overall survival (OS) and BM progression-free survival (BM-PFS) were analyzed using the Kaplan-Meier method and log-rank test. A Cox regression model was used to calculate the hazard ratio and 95% CI for prognostic factors for OS among the study population and propensity score (PS)-matched patients. A BED of 47.4 was taken as the optimal cutoff value. Both OS and BM-PFS were significantly improved in the high-BED (>47.4 Gy) than in the low-BED (≤47.4 Gy) group (median OS: 17.5 months vs 9.5 months, P < .001, median BM-PFS: 14.4 months vs 8.3 months, P < .001). Biologically effective dose (P < .001), Eastern Cooperative Oncology Group performance status (P = .047), smoking (P = .005), and pleural effusion (P = .004) were independent prognostic factors for OS. Propensity score matching with a ratio of 1:2 resulted in 57 patients in the high-BED group and 106 patients in the low-BED group. In the PS-matched cohort, OS and BM-PFS were significantly prolonged in the high-BED group compared with the low-BED group (P < .001). Biologically effective dose >47.4 Gy improves survival among patients with BM from SCLC. Eastern Cooperative Oncology Group score, smoking, and pleural effusion independently affect OS of SCLC patients with BM.

Survival outcomes in an older US population with advanced melanoma and central nervous system metastases: SEER-Medicare analysis.

BACKGROUND: Central nervous system (CNS) metastasis is common in advanced melanoma patients. New treatment options have improved overall prognosis, but information is lacking for patients with CNS metastases. We investigated treatment patterns and survival outcomes in older melanoma patients with and without CNS metastases. METHODS: A retrospective analysis of SEER-Medicare, a population-based linked database, was undertaken in patients aged > 65 years with advanced melanoma diagnosed from 2004 to 2011 and followed until 2013. RESULTS: A total of 2522 patients were included. CNS metastases were present in 24.8% of patients at initial metastatic diagnosis; 16.5% developed CNS metastases during follow-up. Chemotherapy was the most common treatment regardless of CNS metastases. Overall survival (OS) was better for patients without CNS metastases (median, 9.5 months; 95% confidence interval [CI], 8.8-10.2) vs patients with CNS metastases (3.63 months; 95% CI, 3.4-3.9). Among patients with CNS metastases, median OS for targeted therapy, immunotherapy, and chemotherapy was 6 (95% CI, 2.5-9.6), 5.5 (95% CI, 3.8-7.5), and 4.5 (95% CI, 3.8-5.4) months, respectively, vs 2.4 (95% CI, 2.1-2.7) and 2.1 (95% CI, 1.8-2.7) months for local radiotherapy and no treatment, respectively. Stereotactic radiosurgery demonstrated higher OS vs whole-brain radiation therapy (median, 4.98 [95% CI, 3.5-7.5] vs 2.4 [95% CI, 2.1-2.7] months). CONCLUSION: Patients with CNS metastases from melanoma remain a population with high unmet medical need despite recent advances in treatment. Systemic treatments (eg, BRAF-targeted therapy and immunotherapy) and stereotactic radiosurgery demonstrated meaningful but modest improvements in OS. Further explorations of combinations of radiotherapy, BRAF-targeted therapies, and immunotherapies are needed.

A meta-analysis on surgery with or without postoperative radiotherapy to treat squamous cell esophageal carcinoma.

BACKGROUND: Esophageal cancer (EC) is the sixth most common cause of cancer-related mortality in the world. Currently, surgery is the recommended treatment modality when possible. The outcomes of surgery alone are poor, and postoperative radiotherapy (PORT) has been used to patients with esophageal squamous cell carcinoma (ESCC) for years. However, the value of PORT for patients with ESCC after curative resection remains controversial. To assess the benefits and harms of postoperative radiotherapy compared with surgery alone for patients with ESCC we performed in this meta-analysis. METHOD: A comprehensive electronic literature search was performed via the Cochrane Library, MEDLINE and EMBASE from January 1st, 1990 to October 1st, 2018 for relevant trials. The primary outcomes of interest are overall survival (OS) and disease-free survival (DFS). A meta-analysis was performed to calculate the hazard ratio (HR) with 95% confidence interval (CI). RESULTS: Three randomized controlled trials (RCTs) and seven retrospective studies (RS) were included, for a total of 5640 patients with 1774 in the PORT group and 3866 in the surgery alone group respectively. Meta-analysis showed there were significant increases both for OS (HR 0.86, 95%CI 0.79-0.93, p = 0.0004) and DFS (HR 0.74, 95%CI 0.63-0.87, p = 0.004) for patients administered PORT compared with surgery alone. Regarding the postoperative recurrence, PORT can significantly reduce the local recurrence rate (OR 0.34, 95%CI 0.29-0.40, p < 0.00001), while it showed no difference in distant metastasis (OR 1.09, 95%CI 0.91-1.30, p = 0.37). Subgroup analysis demonstrated PORT can improve the OS for patients with positive lymph node (N+, HR 0.73, 95%CI 0.59-0.90, p < 0.00001), curative resection (R0 resection, HR 0.81, 95%CI 0.73-0.90, p < 0.0001) and T3 stage (HR 0.84, 95%CI 0.80-1.0, p = 0.05). CONCLUSIONS: PORT improved the OS and DFS for patients with ESCC compared with surgery alone, and significantly reduced the local recurrence. PORT showed survival benefits for specific subgroups such as patients with positive lymph node, R0 resection margin and T3 stage.