Competing Risk Analysis of Outcomes of Unresectable Pancreatic Cancer Patients Undergoing Definitive Radiotherapy

PurposeWe investigated potential factors, including clinicopathological features, treatment modalities, neutrophil-to-lymphocyte ratio (NLR), carbohydrate antigen (CA) 19-9 level, tumor responses correlating with overall survival (OS), local progression (LP), and distant metastases (DMs), in patients with locally advanced pancreatic cancer (LAPC) who received definitive radiotherapy (RT).MethodsWe retrospectively analyzed demographic characteristics; biologically effective doses (BED10, calculated with an α/β of 10) of RT; and clinical outcomes of 57 unresectable LAPC (all pancreatic adenocarcinoma) patients receiving definitive RT using modern techniques with and without systemic therapy between January 2009 and March 2019 at our institution. We used Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 to evaluate the radiographic tumor response after RT. The association between prognostic factors and OS was assessed using the Kaplan–Meier analysis and a Cox regression model, whereas baseline characteristics and treatment details were collected for competing-risk regression of the association with LP and DM using the Fine–Gray model.ResultsA median BED10 of 67.1 Gy resulted in a disease control rate of 87.7%, and the median OS was 11.8 months after a median follow-up of 32.1 months. The 1-year OS rate, cumulative incidences of LP, and DM were 49.2%, 38.5%, and 62.9%, respectively. Multivariate analyses showed that pre-RT NLR ≥3.5 (adjusted hazard ratio [HR] = 8.245, p < 0.001), CA19-9 reduction rate ≥50% (adjusted HR = 0.261, p = 0.005), RT without concurrent chemoradiotherapy (adjusted HR = 5.903, p = 0.004), and administration of chemotherapy after RT (adjusted HR = 0.207, p = 0.03) were independent prognostic factors for OS. Positive lymph nodal metastases (adjusted subdistribution HR [sHR] = 3.712, p = 0.003) and higher tumor reduction after RT (adjusted sHR = 0.922, p < 0.001) were significant prognostic factors for LP, whereas BED10 ≥ 67.1 Gy (adjusted sHR = 0.297, p = 0.002), CA19-9 reduction rate ≥50% (adjusted sHR = 0.334, p = 0.023), and RT alone (adjusted sHR = 2.633, p = 0.047) were significant prognostic factors for DM.ConclusionOur results indicate that pre-RT NLR and post-RT monitoring of CA19-9 and tumor size reduction can help identify whether patients belong to the good or poor prognostic group of LAPC. The incorporation of new systemic treatments during and after a higher BED10 RT dose for LAPC patients is warranted.

High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy

Purpose Tumor mutational burden (TMB) is a surrogate biomarker of neo-antigens and high TMB status is associated with favorable response to immune-checkpoint inhibitors (ICIs). This study aimed to elucidate the association between TMB and the outcome of definitive radiotherapy in patients with cervical cancer. Materials and methods TMB and treatment outcome were retrospectively analyzed in patients with newly diagnosed cervical cancer treated with definitive radiotherapy available with somatic mutation data of pre-treatment tumors obtained using a commercially available gene panel. Results The study enrolled 98 patients (median follow-up period, 61 months). The median TMB was 9.5 mutations per megabase (range, 3.0–35.5 mutations per megabase). After dichotomization based on this median value, the 5-year overall survival (OS) for TMB-high patients was significantly worse than that of TMB-low patients (61.1% vs. 82.2%). Multivariate analysis identified high TMB status as a significant prognostic factor for worse OS, along with advanced stage, para-aortic lymph node involvement, and absence of concurrent chemotherapy. Conclusion These data indicate that TMB is a potential prognostic factor for worse survival in patients with cervical cancer treated with definitive radiotherapy, thereby providing a rationale for treatment of TMB-high cervical cancers with a combination of ICIs plus radiotherapy. Secondary abstract This retrospective study of 98 patients demonstrates for the first time that tumor mutational burden (TMB) is an independent prognostic factor for worse overall survival of patients treated with definitive radiotherapy, providing a rationale for treatment of TMB-high cervical cancers with a combination of immune-checkpoint inhibitors plus radiotherapy.

Management and Outcomes of Patients With Radiotherapy Interruption During the COVID-19 Pandemic

PurposeThis retrospective observational study examined patients who experienced radiotherapy (RT) interruption during the Wuhan lockdown for the novel coronavirus disease 2019 (COVID-19) pandemic.Materials and MethodsThe data of all patients whose RT was interrupted during the Wuhan lockdown from January 23 to April 8, 2020 were collected. Patient-, cancer-, and treatment-related characteristics were analyzed, along with interruption time, disease progression type, and survival status. The methods employed in order to compensate for RT interruption were also described.ResultsThere were altogether 129 cancer patients whose RT was interrupted. Nineteen (14.7%) patients experienced a total interruption time of at most 7 days; the interruption time was 8–14 days for 27 (20.9%) patients, and 15 or more days for 47 (36.4%) patients. The remaining 36 (27.9%) patients did not come back to our hospital for further RT. We first describe our experience with re-immobilization and/or re-planning (n = 17) as well as dose compensation/adjustment. Of the 40 definitive radiotherapy patients, 37 had squamous cell carcinoma of nasopharyngeal, lung, or cervical origin. Most patients (85/93, 91.4%) were followed up for more than one year. Among the 40 patients who received definitive radiotherapy, nine patients experienced disease progression and five patients died. Three of the seven (42.9%) patients who did not finish radiotherapy after interruption died, as compared to only two of the 33 (6.1%) patients who completed radiotherapy. EQD2 (equivalent dose in 2 Gy fractions) at the time point of RT interruption was calculated. Five of the six patients (83.3%) who received EQD2 ≤10 Gy suffered from disease progression, compared with four of the 34 (11.8%) patients who received EQD2 >10 Gy. For the seven definitive radiotherapy cases who did not finish radiotherapy, three received systemic anti-cancer treatments and three died (all of whom did not receive further systemic therapies).ConclusionsThis study provides the longest follow-up for the outcomes of RT interruption during COVID-19 pandemic to date. It cannot imply causation but implies that completing RT is important, along with the utility of having patients remain on systemic therapies if RT is to be interrupted.

Definitive radiotherapy for squamous cell carcinoma of the oral cavity: a single-institution experience

Background Surgery is standard of care for oral cavity cancer (OCC). We provide a single-institution experience using definitive radiotherapy (RT) with or without concurrent systemic therapy for primary unresectable OCC. Patients and methods We retrospectively examined 49 patients with non-metastatic primary unresectable OCC treated with definitive RT between 2000 and 2019. The majority of patients (63.3%) were treated with definitive chemoradiotherapy while 26.5% were given single-agent cetuximab weekly simultaneous to definitive RT. Five patients were treated with definitive RT alone because of limited disease and no nodal involvement. Results Median follow-up was 73 months (range, 6–236 months), median progression free survival (PFS) was 42 months (range, 2–157 months), median local disease-free survival (LDFS) was 44 months (range, 2–157 months) and median overall survival (OS) from the time of RT initiation was 52 months (range, 5–236 months). There were 65.3% locoregional failures, 84.4% local and 15.6% distant metastasis. The majority of patients with local failure presented with American Joint Committee on Cancer (AJCC) Stage III–IV disease (59.2%). The 5-year Kaplan-Meier estimates for OS (III–IV vs. I–II) was 22.8% vs. 54.2 % (p = 0.03, HR 2.090, 1.1–4.2). Patients who were treated with systemic therapy had a significant better 5-year overall survival compared to those with RT alone (43.9% vs. 23.1%, p = 0.05, 1.0–4.1). RT with doses less than 70 Gy (p = 0.046, HR 2.1 (1.0–4.5) was associated with worse overall survival. Mucositis was the most common ≥ grade 3 acute toxicity and occurred in 19 patients (39%). Incidences of chronic toxicities were loss of taste, trismus, osteoradionecrosis and xerostomia. Conclusions Definitive RT with or without concurrent systemic agents in patients with unresectable OCC resulted in an eloquent rate of locoregional control and good overall survival rates and is currently the best available treatment option in this patient collective.