Survival Comparisons between Breast Conservation Surgery and Mastectomy Followed by Postoperative Radiotherapy in Stage I-III Breast Cancer Patients: Analysis of the Surveillance, Epidemiology, and End Results (Seer) Program Database.

Background: This study aims to evaluate the overall and breast cancer-specific survival (BCSS) after breast-conserving surgery (BCS) plus radiotherapy (RT) compared with mastectomy plus RT in resectable breast cancer. Moreover, the aim is to also identify the subgroups who benefit from BCS plus RT and establish a predictive nomogram for stage II patients. Methods: Stage I−III breast cancer patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 1990 and 2016. Patients with available clinical information were split into two groups: BCS plus RT and mastectomy plus RT. Kaplan−Meier survival analysis, univariate and multivariate regression analysis, and propensity score matching were used in the study. Hazard ratio (HR) was calculated based on stratified Cox univariate regression analyses. A prognostic nomogram by multivariable Cox regression model was developed for stage II patients, and consistency index (C-index) and calibration curve were used to evaluate the accuracy of the nomogram in the training and validation set. Results: A total of 24,590 eligible patients were enrolled. The difference in overall survival (OS) and BCSS remained significant in stage II patients both before and after PSM (after PSM: OS: HR = 0.8536, p = 0.0115; BCSS: HR = 0.7803, p = 0.0013). In stage II patients, the survival advantage effect of BCS plus RT on OS and BCSS was observed in the following subgroups: any age, smaller tumor size (<1 cm), stage IIA (T2N0, T0−1N1), ER (+), and any PR status. Secondly, the C-indexes for BCSS prediction was 0.714 (95% CI 0.694−0.734). The calibration curves showed perfect agreement in both the training and validation sets. Conclusions: BCS plus RT significantly improved the survival rates for patients of stage IIA (T2N0, T0−1N1), ER (+). For stage II patients, the nomogram was a good predictor of 5-, 10-, and 15-year BCSS. Our study may help guide treatment decisions and prolong the survival of stage II breast cancer patients.

Overview of adjuvant radiotherapy on survival, failure pattern and toxicity in stage I to II endometrial carcinoma: a long-term multi-institutional analysis in China.

BACKGROUND: This research aimed to provide an overview of the impact of adjuvant vaginal brachytherapy (VBT) and external beam pelvic radiotherapy (EBRT) with or without VBT on survival in stage I to II EC patients in China from a long-term multi-institutional analysis. METHODS: We retrospectively analyzed stage I to II EC patients from 13 institutions treated between 2003 and 2015. All patients underwent surgical staging and received adjuvant RT. Patients were divided into groups of low-risk (LR), intermediate-risk (IR), high-intermediate-risk (HIR) and high-risk (HR). Survival statistics, failure pattern, and toxicity of different radiation modalities in different risk groups were analyzed. RESULTS: A total of 1048 patients were included. HR disease represented 27.6%, HIR 17.7%, IR 27.7% and LR 27.1%, respectively. Endometrioid adenocarcinoma (EAC) and non-endometrioid carcinoma (NEC) accounted for 92.8 and 7.2%. A total of 474 patients received VBT alone and 574 patients received EBRT with or without VBT. As for EAC patients, the 5-year overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rate was: 94.6, 90.4, 93.0 and 91.6%, respectively. For LR patients, EBRT (with or without VBT) seemed to be a risk factor. With the higher risk category, the survival benefit of EBRT gradually became remarkable. EBRT (with or without VBT) significantly increased DFS, LRFS and DMFS compared to VBT alone in the HR group (p < 0.05). Distant metastasis was the main failure pattern for all risk groups. As for NEC patients, the 5-year OS, DFS, LRFS and DMFS rate was: 93.4, 87.2, 91.7 and 89.3%, respectively. As for toxicity, EBRT (with or without VBT) significantly increased the incidence of grade 1-2 gastrointestinal, urinary, and hematological toxicity. CONCLUSIONS: For stage I to II EC patients, EAC accounted for the majority and had better prognosis than NEC. For EAC patients, VBT alone resulted in comparable survival to EBRT in the LR, IR and HIR groups, while EBRT significantly increased survival in the HR group. EBRT had higher rate of toxicity than VBT.

Sacral Chordoma: A Population-based Analysis of Epidemiology and Survival Outcomes.

BACKGROUND/AIM: Sacral chordoma is a rare primary bone neoplasm associated with high morbidity. The aim of this study is to identify demographic and clinicopathological characteristics of this tumor and evaluate their impact on survival outcomes. PATIENTS AND METHODS: The Surveillance, Epidemiology and End Results (SEER) database collecting data between 2000 and 2018 was searched for all cases of sacral chordoma. We analyzed demographic aspects, cancer stage and treatment patterns. Overall survival was calculated using the Kaplan-Meier method and compared between subgroups using the log-rank test. A multivariate Cox hazard regression analysis was conducted to identify independent predictors of overall survival. RESULTS: Four hundred and forty-two patients were identified with a mean age of 62.7 years. Most tumors presented regional invasion at diagnosis (43.2%). Mean overall survival was 124.7 months. No significant difference in terms of overall survival was found between surgery alone and surgery associated with radiotherapy. Both options provided a significantly increased survival than radiotherapy alone. Age of less than 50 years or between 50 and 69 correlated significantly with improved survival. CONCLUSION: Age and stage at diagnosis impact significantly survival outcomes. Surgery remains the mainstay treatment with the highest overall survival. Its association with radiotherapy is currently questionable and needs further research.

Adjuvant Therapy and Prognosticators of Survival in Head and Neck Mucosal Melanoma.

OBJECTIVES/HYPOTHESIS: To identify prognosticators and determine the efficacies of surgery with adjuvant radiotherapy (SR) and surgery with immunotherapy (SI) of head and neck mucosal melanoma (HNMM). STUDY DESIGN: Retrospective database study. METHODS: The 2004 to 2017 National Cancer Database was queried for HNMM patients. Cox proportional hazards and Kaplan-Meier analyses evaluated prognosticators of mortality and survival benefits conferred by SR, SI, or surgery with adjuvant radiotherapy and immunotherapy (SRI). Logistic regression identified predictors of adjuvant radiotherapy or immunotherapy use. RESULTS: Overall, 1,910 cases (845 surgery, 802 SR, 51 SI, 101 SRI) were analyzed, with 50.3% females and an average age of 68.6 ± 13.8 years. SI was associated with greater overall survival (OS) than surgery (hazard ratio [HR] 0.672; P = .036). SI (HR 0.425; P = .024) and SRI (HR 0.594; P = .045) were associated with superior OS than SR. Older age (HR 1.607; P < .001), female sex (HR 0.757; P = .006), paranasal sinus localization (HR 1.648; P < .001), T4 classification (HR 1.443; P < .001), N1 classification (HR 2.310; P < .001), M1 classification (HR 3.357; P < .001), and positive surgical margins (HR 1.454; P < .001) were survival prognosticators. Adjuvant radiotherapy use was negatively correlated with older age, oral cavity localization, and M0 or T3 tumors (all P < .05). Adjuvant immunotherapy use was positively correlated with younger age and M1 tumors (all P < .05). CONCLUSIONS: Although SR did not confer survival benefits in HNMM patients, SI and SRI yielded greater OS than surgery alone. SRI was associated with superior survival outcomes than SR. Certain demographic and clinical factors were associated with increased mortality risk. Patient age and certain tumor characteristics were predictors of adjuvant radiotherapy or immunotherapy use. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:584-592, 2022.

Absence of Survival Improvement for Patients with Esthesioneuroblastoma Over the Past 2 Decades: A Population-Based Study.

OBJECTIVE: Esthesioneuroblastoma (ENB) is a rare malignancy of the sinonasal tract and its infrequency has confounded efforts at clearly describing the survival trends associated with this neoplasm over the years. In this study, we reviewed survival trends in ENB and investigated the impact of treatment extent and modality on patient outcomes. METHODS: We accessed the Surveillance, Epidemiology, and End Result (SEER) program to identify ENB cases from 1998 to 2016. A χ2 test was used to compare the categorical covariates and a t test or Mann-Whitney U test was utilized for continuous variables. The impact of prognostic factors on survival was computed using a Kaplan-Meier analysis and multivariate Cox proportional hazards model. We divided ENB patients into 4 periods including 1998-2002, 2003-2007, 2008-2012, and 2013-2016, and investigated survival trends using the Kaplan-Meier curve and log-rank test. RESULTS: ENB patients who underwent biopsy alone were associated with older age, larger tumor diameter, increased rates of tumor extension, nodal/distant metastases, and advanced stages as compared with patients undergoing tumor resection. Our results also demonstrated that surgical resection and adjuvant radiotherapy could confer survival advantages, whereas chemotherapy was associated with reduced survival in patients with ENB. Over the past 2 decades, surprisingly, there has been no change in survival rates for patient with ENB (P = 0.793). CONCLUSIONS: Despite advanced diagnostic studies and modernized treatment approaches, ENB survival has remained unchanged over the years, calling for improved efforts to develop appropriate individualized interventions for this rare tumor entity. Our results also confirmed that surgery and adjuvant radiotherapy is associated with improved patient survival whereas the use of chemotherapy should be considered carefully.

Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation in stage IV rectal cancer patients with potentially resectable metastases.

BACKGROUND: The optimal treatment of stage IV rectal cancer remains controversial. The purpose of this study was to assess the treatment outcomes and toxicity of neoadjuvant chemotherapy and radiotherapy followed by local treatment of all tumor sites and subsequent adjuvant chemotherapy in stage IV rectal cancer patients with potentially resectable metastases. METHODS: Adult patients diagnosed with locally advanced rectal adenocarcinoma with potentially resectable metastases, who received neoadjuvant chemotherapy and radiotherapy from July 2013 and September 2019 at Sun Yat-sen University cancer center, were included. Completion of the whole treatment schedule, pathological response, treatment-related toxicity and survival were evaluated. RESULTS: A total of 228 patients were analyzed with a median follow-up of 33 (range 3.3 to 93.4) months. Eventually, 112 (49.1%) patients finished the whole treatment schedule, of which complete response of all tumor sites and pathological downstaging of the rectal tumor were observed in three (2.7%) and 90 (80.4%) patients. The three-year overall survival (OS) and progression-free survival (PFS) of all patients were 56.6% (50.2 to 63.9%) and 38.6% (95% CI 32.5 to 45.8%), respectively. For patients who finished the treatment schedule, 3-year OS (74.4% vs 39.2%, P < 0.001) and 3-year PFS (45.5% vs 30.5%, P = 0.004) were significantly improved compared those who did not finish the treatment. Grade 3-4 chem-radiotherapy treatment toxicities were observed in 51 (22.4%) of all patients and surgical complications occurred in 22 (9.6%) of 142 patients who underwent surgery, respectively. CONCLUSIONS: Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation and subsequent adjuvant chemotherapy offered chances of long-term survival with tolerable toxicities for selected patients with potentially resectable stage IV rectal cancer, and could be considered as an option in clinical practice.

Additional Radiotherapy With or Without Chemotherapy Following Endoscopic Resection for Stage I Esophageal Carcinoma: A Pilot Study.

Objective: To evaluate the safety and efficacy of additional radiotherapy after endoscopic resection (ER) for stage I esophageal carcinoma (EC) with high-risk factors. Materials and methods: Patients with stage cT1N0M0 EC who underwent ER and additional radiotherapy between January 2010 and August 2019 at our institution were retrospectively included. Overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), local control rate, regional control rate, common acute toxicities, esophageal stricture, and dysphagia were analyzed. Results: Thirty-one consecutive patients were included in the study. The median age was 62 years (range, 49-78). Thirty patients (96.8%) had squamous cell carcinoma, and one patient (3.2%) had adenosquamous cell carcinoma. Twenty-six patients (83.9%) had submucosal invasion, 15 patients (48.4%) had lymphovascular invasion, and one patient (3.2%) had a venous invasion. The 1-, 3-, and 5-year OS rates were 100.0%, 86.9%, and 68.5%, respectively. The corresponding DFS rates were 100.0%, 85.2%, and 75.8%, respectively. The corresponding CSS rates were 100.0%, 89.8%, and 78.6%, respectively. The local and regional control rates were 100.0% and 93.5%, respectively. No grade 4-5 acute toxicities were observed. Fifteen patients (48.4%) were endoscopically diagnosed with esophageal strictures after ER. At the last follow-up, 28 patients (90.5%) were able to eat a regular diet, one patient (3.2%) could eat a soft diet, one needed a semifluid diet, and only one (3.2%) had to eat a fluid diet. Conclusions: For patients with stage I EC, additional radiotherapy following ER is safe and effective, with the swallowing function well-preserved. Nevertheless, prospective studies are needed to verify these results.

Safety profile and clinical outcome of adjuvant radiation therapy and intermediate-dose interferon in comparison with intermediate-dose interferon alone in patients with melanoma metastases in regional lymph nodes and unfavorable prognostic factors.

AIM: To assess the safety profile and efficacy of adjuvant radiation therapy and intermediate-dose interferon in comparison with intermediate-dose interferon alone in patients with synchronous and metachronous skin melanoma metastases in regional lymph nodes with unfavorable prognostic factors. MATERIALS AND METHODS: 96 patients with synchronous and metachronous skin melanoma metastases in regional lymph nodes (stage III according to American Joint Committee on Cancer) and unfavorable prognostic factors were randomized in 2 groups: one of them (n = 45) received regional radiation therapy 50-55 Gy and intermediate dose of α2b-interferon (RT + IFN) in adjuvant setting and another one (n = 51) intermediate dose of α2b-interferon alone (IFN). RESULTS: The most common adverse events in both groups were pyrexia and fatigue but grades 3-4 were observed more frequently in the RT + IFN group than in the IFN group (24.4 and 42.2% vs 11.8 and 27.5% respectively). 3-year recurrence-free survival was 78.5% in the RT + IFN group and 73.8% in the IFN group (p = 0.72), 3-year progression-free survival was 63.2% in the RT + IFN group comparing with 57.2% in the IFN group (p = 0.59) and 3-year overall survival was 77.1% and 66.7%, respectively (p = 0.29). Median of recurrence-free, progression-free and overall survival was not reached in any group. CONCLUSIONS: Radiation therapy and intermediate-dose interferon in adjuvant setting tends to improve recurrence-free, progression-free and overall survival comparing with intermediate-dose interferon alone in patients with synchronous and metachronous skin melanoma metastases in regional lymph nodes and unfavorable prognostic factors but it needs further investigation in larger groups of patients.

Radiotherapy for Primary Tracheal Carcinoma: Experience at a Single Institution.

BACKGROUND: There is limited understanding of tracheal carcinoma (TC) because of its rarity. We examined the efficacy of radiotherapy (RT) for patients with primary TC. METHODS: We analyzed the records of 32 patients with primary TC who received RT at our center between November 1996 and December 2016. RESULTS: Thirteen patients received adjuvant RT and 18 received definitive RT. Eight patients achieved complete remission (CR) after definitive RT. Among all patients, the 5-year overall survival (OS) rate was 46.9% and the locoregional progression free survival (LRPFS) rate was 68.1%. Univariate analysis indicated the 5-year OS was better in those with adenoid cystic adenocarcinoma than squamous cell carcinoma (P = 0.001); the 5-year LRPFS was better in patients who received surgical resection than those who did not (92.9% vs 46.4%, P = 0.013) and in patients who received postoperative RT than in those who received definitive RT (91.7% vs 50.1%, P = 0.038). A sub-group univariate analysis indicated the 5-year PFS was better for those who received at least 68 Gy of radiation (44.4% vs 13.0%, P = 0.044). Patients who achieved CR had a better 5-year PFS than those who did not (57.1% vs 10%, P = 0.006). No patients had a toxicity of grade 3 or more. CONCLUSIONS: Adjuvant and definitive RT are safe and effective treatments for TC. Patients who received dosages of 68 Gy or more and who had complete tumor regression following definitive RT seemed to have better long-term survival.

The value of primary and adjuvant radiotherapy for cutaneous squamous cell carcinomas of the head-and-neck region in the elderly.

PURPOSE: To examine treatment patterns, oncological outcomes and toxicity rates in elderly patients receiving radiotherapy for cutaneous squamous cell carcinoma (cSCC) of the head-and-neck region. MATERIAL AND METHODS: In this retrospective single-center analysis, locoregional control (LRC), progression-free survival (PFS) and overall survival (OS) of elderly patients > 65 years with cSCC of the head-and-neck region undergoing radiotherapy between 2010 and 2019 were calculated. The prognostic value of clinicopathological parameters on radiotherapy outcomes was analyzed using the Cox proportional hazards model. In addition, both acute and chronic toxicities were retrospectively quantified according to CTCAE version 5.0. RESULTS: A total of 69 elderly patients with cSCC of the head-and-neck region with a median age of 85 years were included in this analysis, of whom 21.7% (15 patients) presented with nodal disease. The majority of patients exhibited a good performance status, indicated by a median Karnofsky performance status (KPS) and Charlson Comorbidity Index (CCI) of 80% and 6 points, respectively. Radiotherapy was administered as primary (48%), adjuvant (32%) or palliative therapy (20%). 55 patients (79.7%) completed treatment and received the scheduled radiotherapy dose. Median EQD2 radiation doses were 58.4 Gy, 60 Gy and 51.3 Gy in the definitive, adjuvant and palliative situation, respectively. 2-year LRC, PFS and OS ranged at 54.2%, 33.5 and 40.7%, respectively. Survival differed significantly between age groups with a median OS of 20 vs. 12 months (p < 0.05) for patients aged 65-80 or above 80 years. In the multivariate analysis, positive lymph node status remained the only significant prognostic factor deteriorating OS (HR 3.73, CI 1.54-9.03, p < 0.01). Interestingly, neither KPS nor CCI impaired survival in this elderly patient cohort. Only 3 patients (4.3%) experienced acute CTCAE grade 3 toxicities, and no chronic CTCAE grade 2-5 toxicities were observed in our cohort. CONCLUSION: Radiotherapy was feasible and well-tolerated in this distinct population, showing the general feasibility of radiotherapy for cSCC of the head-and-neck region also in the older and oldest olds. The very mild toxicities may allow for moderate dose escalation to improve LRC.

Outcome of hypofractionated breast irradiation and intraoperative electron boost in early breast cancer: A randomized non-inferiority clinical trial.

BACKGROUND: Intraoperative electron radiotherapy (IOERT) followed by hypofractionated whole breast irradiation (HWBI) provides the shortest possible time of adjuvant breast irradiation. The efficacy of either method has been described in previous reports; however, to our knowledge, the efficacy of combined therapy has not been reported. AIM: To compare the toxicity and cosmetic outcome of IOERT as a tumor bed boost followed by HWBI with conventional whole breast irradiation (CWBI) followed by external electron tumor bed boost (EETBB) after breast conserving surgery (BCS) in patients with invasive breast cancer. METHODS: In 2019, a prospective noninferiority trial (IRCT20180919041070N2) was started. After BCS, early-stage breast cancer patients were treated by IOERT (10 Gy) and HWBI (42.56 Gy in 16 fractions) or CWBI (50 Gy in 25 fraction) and EETBB (10 Gy in 5) in a double-arm design. Acute/late toxicity and cosmetic outcome were evaluated by common toxicity criteria (CTC) after 1-year follow-up (FUP) at the level of p < .05. RESULTS: Of 60 eligible patients, 30 were allocated to each group. Regarding acute effects after a median FUP of 12 months, CTC-score of grade II-III erythema (p = .001) and desquamation (p = .005) were significantly higher in CWBI+EETBB compared to IOERT+ HWBI. However, there were no significant differences at the end of radiotherapy and after 1 month, 6 months, and 1 year. Cosmetic outcome after radiation was similar in both groups mostly rating as good/excellent after 1-year FUP. CONCLUSIONS: Boost-IOERT/HWBI regimen has comparable acute and late treatment toxicity profiles compared to the CWBI.

Unique prognostic features of grade 3 endometrioid endometrial carcinoma: Findings from 101 consecutive cases at a Japanese tertiary cancer center.

OBJECTIVE: The prognosis of and optimal treatment for grade 3 endometrioid endometrial carcinoma (G3EEC) currently remain unclear. This study aimed to clarify the baseline recurrence risk in patients with early-stage (stage I-II) G3EEC without adjuvant therapy and the prognosis of patients with advanced-stage (stage III-IV) G3EEC. MATERIALS AND METHODS: A total of 101 patients with pathologically confirmed G3EEC from 1997 to 2018 were identified. Their clinicopathological characteristics and survival outcomes were reviewed retrospectively. Disease-free survival and overall survival values were estimated according to the Kaplan-Meier method and compared using a log-rank test. RESULTS: Recurrence was observed in eight (13%) of 63 patients with early-stage G3EEC, none of whom had received adjuvant therapy. The 5-year disease-free survival and 5-year overall survival rates for these patients were 86.7% and 96.4%, respectively. Recurrence was also observed in 12 (41%) of 29 patients with stage III G3EEC. The 5-year overall survival rates for stage III patients who underwent adjuvant chemotherapy and adjuvant radiotherapy were 85.6% and 42.9%, respectively. The 3-year overall survival rate among stage IVB patients was only 12.7% despite multidisciplinary treatment provision. CONCLUSION: Our study newly demonstrates that patients with early-stage G3EEC have a favorable prognosis and a low recurrence rate in the absence of adjuvant therapy. In patients with stage III G3EEC, adjuvant chemotherapy was more beneficial than adjuvant radiotherapy. The poor prognosis of patients with stage IV G3EEC indicates the need for more effective treatments. Unique therapeutic approaches based on staging are recommended for treatment of G3EEC.

A Multi-Institutional Analysis of Adjuvant Chemotherapy and Radiation Sequence in Women With Stage IIIC Endometrial Cancer.

PURPOSE: Our purpose was to evaluate the effect of sequence and type of adjuvant therapy for patients with stage IIIC endometrial carcinoma (EC) on outcomes. METHODS AND MATERIALS: In a multi-institutional retrospective cohort study, patients with stage IIIC EC who had surgical staging and received both adjuvant chemotherapy and radiation therapy (RT) were included. Adjuvant treatment regimens were classified as adjuvant chemotherapy followed by sequential RT (upfront chemo), which was predominant sequence; RT with concurrent chemotherapy followed by chemotherapy (concurrent); systemic chemotherapy before and after RT (sandwich); adjuvant RT followed by chemotherapy (upfront RT); or chemotherapy concurrent with vaginal cuff brachytherapy alone (chemo-brachy). Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method. RESULTS: A total of 686 eligible patients were included with a median follow-up of 45.3 months. The estimated 5-year OS and RFS rates were 74% and 66%, respectively. The sequence and type of adjuvant therapy were not correlated with OS or RFS (adjusted P = .68 and .84, respectively). On multivariate analysis, black race, nonendometrioid histology, grade 3 tumor, stage IIIC2, and presence of adnexal and cervical involvement were associated with worse OS and RFS (all P < .05). Regardless of the sequence of treatment, the most common site of first recurrence was distant metastasis (20.1%). Vaginal only, pelvic only, and paraortic lymph node (PALN) recurrences occurred in 11 (1.6%),15 (2.2 %), and 43 (6.3 %) patients, respectively. Brachytherapy alone was associated with a higher rate of PALN recurrence (15%) compared with external beam radiation therapy (5%) P < .0001. CONCLUSIONS: The sequence and type of combined adjuvant therapy did not affect OS or RFS rates. Brachytherapy alone was associated with a higher rate of PALN recurrence, emphasizing the role of nodal radiation for stage IIIC EC. The vast proportion of recurrences were distant despite systemic chemotherapy, highlighting the need for novel regimens.

Additional radiotherapy to breast-conserving surgery is an optional treatment for de novo stage IV breast cancer: A population-based analysis.

BACKGROUND: We aim to assess the value of locoregional treatment (LRT) including breast-conserving surgery (BCS), mastectomy (MAST), and radiotherapy (RT) in patients with de novo stage IV breast cancer. METHODS: Patients with de novo stage IV breast cancer were retrospectively identified from the Surveillance, Epidemiology, and End Results database between 2004 and 2014. Kaplan-Meier analysis, log-rank tests, propensity score matching (PSM), and the multivariate Cox proportional model were used for statistical analysis. RESULTS: A total of 5798 patients were identified including 849 (14.6%), 763 (13.2%), 2338 (40.3%), and 1848 (31.9%) who received BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively. The proportions of receiving BCS decreased from 35.9% in 2004 to 26.2% in 2014 (p = 0.002), and the probability of patients receiving MAST increased from 64.1% in 2004 to 74.8% in 2014 (p = 0.002). Before PSM, there was a significant difference in breast cancer-specific survival (BCSS) among the treatment arms. Patients who received RT had better BCSS, the 5-year BCSS was 40.5%, 52.3%, 41.5%, and 47.7% in patients treated with BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively (p < 0.001). In the PSM cohort, patients treated with BCS alone had lower 5-year BCSS compared to those treated with BCS+RT (43.9% and 52.1%, p = 0.002). However, there were comparable 5-year BCSS between BCS+RT and MAST alone groups (51.3% and 50.1%, p = 0.872), and BCS+RT and MAST+RT cohorts (51.5% and 55.7%, p = 0.333). Similar results were confirmed in multivariate analysis. CONCLUSIONS: Postoperative RT improves BCSS in patients with de novo stage IV breast cancer, and BCS+RT shows a non-inferior outcome compared to MAST+RT. BCS+RT may be the optimal local management of de novo stage IV breast cancer.

Utility of adjuvant whole abdominal radiation therapy in ovarian clear cell cancer (OCCC): a pragmatic cohort study of women with classic immuno-phenotypic signature.

BACKGROUND: To evaluate the initial experience and clinical utility of first-line adjuvant intensity-modulated whole abdominal radiation therapy (WART) in women with ovarian clear cell cancer (OCCC) referred to an academic center. METHODS: Progression-free and overall survival was analyzed in a pragmatic observational cohort study of histologically pure OCCC patients over-expressing HNF-1ß treated between 2013 and end-December 2018. An in-house intensity-modulated WART program was developed from a published pre-clinical model. Radiation dose-volume data was curated to American Association of Physics in Medicine (AAPM) Task Group 263 recommendations. A dedicated database prospectively recorded presenting characteristics and outcomes in a standardized fashion. RESULTS: Five women with FIGO (2018) stage IA to IIIA2 OCCC were treated with first-line WART. Median age was 58 years (range 47-68 years). At diagnosis CA-125 was elevated in 4 cases (median 56 kU/L: range 18.4-370 kU/L) before primary de-bulking surgery. Severe premorbid endometriosis was documented in 3 patients. At a median follow-up of 77 months (range 16-83 mo.), all patients remain alive and progression-free on clinical, biochemical (CA-125), and 18Fluoro-deoxyglucose (FDG) PET/CT re-evaluation. Late radiation toxicity was significant (G3) in 1 case who required a limited bowel resection and chronic nutritional support at 9 months post-WART; 2 further patients had asymptomatic (G2) osteoporotic fragility fractures of axial skeleton at 12 months post-radiation treated with anti-resorptive agents (denosumab). CONCLUSIONS: The clinical utility of intensity-modulated WART in OCCC over-expressing HNF-1ß was suggested in this small observational cohort study. The hypothesis that HNF-1ß is a portent of platinum-resistance and an important predictive biomarker in OCCC needs further confirmation. Curating multi-institutional cohort studies utilizing WART by means of "Big Data" may improve OCCC care standards in the future.

Clear cell histology portends a worse prognosis than other WHO grade II histologies.

PURPOSE: Clear cell meningioma (CCM) is a rare WHO grade II meningioma variant, characterized by aggressive features and a high tumor recurrence rate. In this study, we compared overall and progression-free survivals between CCMs and other WHO grade II meningiomas. METHODS: A retrospective institutional database review was performed to identify all patients who underwent surgical resection of a WHO grade II meningioma between 1997 and 2019. Overall survival and progression-free survival were compared between patients with clear cell meningiomas and patients with other WHO grade II meningiomas. Multivariable Cox proportional-hazards analysis was used to identify independent predictors of tumor recurrence and survival. RESULTS: We included a total of 214 patients in this study (43 CCMs, 171 other WHO grade II meningiomas). Patients with CCMs had significantly shorter progression-free (p = 0.001) and overall (p = 0.026) survivals than patients with other grade II meningiomas. In multivariable analysis, clear cell histology was a significant and powerful independent predictor of tumor recurrence (HR 1.93; 95% CI 1.14-3.26) when controlling for tumor location, extent of resection, and adjuvant radiation. In multivariable analysis, clear cell histology correlated with increased mortality (HR 1.96, 95% CI 0.97-3.94), though this was not statistically significant. CONCLUSION: This is the first study to compare overall and progression-free survivals between CCMs and other WHO grade II meningiomas. Clear cell histology predicts a higher risk of tumor recurrence and mortality than other grade II histologies. Future studies may help to understand the impact of these findings and the treatment implications.

Comparing hypofractionated and conventionally fractionated whole breast irradiation for patients with ductal carcinoma in situ after breast conservation: a propensity score-matched analysis from a national multicenter cohort (COBCG-02 study).

BACKGROUND AND PURPOSE: Randomized trials confirmed the efficacy and the safety of hypofractionated whole breast irradiation (HF-WBI) in patients with early-stage breast cancer. However, the role of HF-WBI in patients with DCIS after breast conserving surgery has not yet been clearly established in prospective randomized trials. The aim of this study was to evaluate if HF-WBI can be considered comparable to conventionally fractionated (CF)-WBI in DCIS patients. MATERIALS AND METHODS: The analysis included DCIS patients from four Italian centers treated with CF-WBI 50 Gy/25 fractions or HFRT 40.5 Gy/15 fractions, without tumor bed boost. A propensity score matching (PSM) analysis was performed using a logistic regression that considered age, grading, presence of necrosis, resection margin status and adjuvant endocrine therapy. RESULTS: Five hundred twenty-seven patients was included (367 in the CF-WBI-group and 160 in the HR-WBI group). After 1:1 matching, 101 patients were allocated to the CF-WBI-group and 104 to the HF-WBI group. No correlation was observed between the type of RT schedule and LRFS (HR 1.68, 95% CI 0.82-3.45; p = 0.152). After PSM, no statistical difference was observed between the two RT group (HR 1.11, 95% CI 0.40-3.04; p = 0.833), with 3- and 5-years LRFS rates of 100% and 97.9% for CF-WBI and 95.6% and 94% for HF-WBI. CONCLUSION: A short course of radiation therapy seems to be comparable to CF-WBI in terms of clinical outcomes. These data support the use of hypofractionated schedules in DCIS patients, but considering the remaining uncertainties.

The Interval Between Preoperative Radiation and Surgery Is Not Associated with Overall Survival for Soft-tissue Sarcomas: An Analysis of the National Cancer Database.

BACKGROUND: Most cancer centers prefer preoperative radiation therapy (preRT) over postoperative therapy to treat soft-tissue sarcoma (STS) to limit long-term fibrosis, joint stiffness, and edema. Surgery is often delayed after preRT to allow for tissue recovery and to reduce wound complications. However, the association between the time interval between preRT and surgery and survival is unknown. QUESTIONS/PURPOSES: (1) What factors are associated with the preRT-surgery interval in patients with STS? (2) Is the preRT-surgery interval associated with overall survival? METHODS: The National Cancer Database, a nationwide registry that includes 70% of all new cancers in the United States with 90% follow-up, was reviewed to identify 6378 patients who underwent preRT and surgical resection for a localized extremity or pelvic STS from 2004 to 2014. Patients were excluded if they had lymphatic or metastatic disease at diagnosis (23%; n = 1438), underwent neoadjuvant chemotherapy (24%; 1531), were missing vital status (8%; 487), had chemosensitive histologies (9%; 603), underwent radiation other than external beam (1%; 92), were missing preRT-surgery interval (1%; 45), or had a preRT-surgery interval greater than 120 days (< 1%; 6). A total of 2176 patients were included for analysis, with a mean preRT-surgery interval of 35 ± 16 days. A multiple linear regression model was generated to assess demographic, clinicopathologic, and treatment characteristics associated with the preRT-surgery interval. A Kaplan-Meier survival analysis was then conducted, stratified by the preRT-surgery interval, to assess survival over 10 years. Finally, a multivariate Cox regression analysis model was constructed to further evaluate the association between the preRT-surgery interval and overall survival, adjusted for demographic, clinicopathologic, and treatment characteristics. RESULTS: A longer preRT-surgery interval was associated with higher age (ß = 0.002 per year [95% CI 0.0 to 0.004]; p = 0.026), tumor location in the pelvis (compared with the lower extremity; ß = 0.15 [95% CI 0.082 to 0.22]; p < 0.001), and malignant peripheral nerve sheath tumor subtype (compared with undifferentiated pleomorphic sarcoma; ß = 0.17 [95% CI 0.044 to 0.29]; p = 0.008). A shorter preRT-surgery interval was associated with higher facility volume (ß = -0.002 per case [95% CI -0.003 to -0.002]; p = 0.026) and higher tumor stage (compared with Stage I; ß = -0.066 [95% CI -0.13 to -0.006]; p = 0.03 for Stage II; ß = -0.12 [95% CI -0.17 to -0.065]; p < 0.001 for Stage III). The 5-year overall survival rates were similar across all preRT-surgery interval groups: less than 3 weeks (66% [95% CI 60 to 72]), 3 to 4 weeks (65% [95% CI 60 to 71]), 4 to 5 weeks (65% [95% CI 60 to 71]), 5 to 6 weeks (66% [95% CI 60 to 72]), 6 to 7 weeks (63% [95% CI 54 to 72]), 7 to 9 weeks (66% [95% CI 58 to 74]), and more than 9 weeks (59% [95% CI 48 to 69]). Over 10 years, no difference in overall survival was observed when stratified by the preRT-surgery interval (p = 0.74). After controlling for potentially confounding variables, including age, sex, Charlson/Deyo comorbidity score, histology, tumor size, stage and surgery type, the preRT-surgery interval was not associated with survival (hazard ratio = 1 per day [95% CI 1 to 1]; p = 0.88). CONCLUSION: With the numbers available, this study demonstrates that a delay in surgery up to 120 days after radiation is not associated with poorer survival. Therefore, clinicians may be able to delay surgery to minimize the risks of wound complications and modifiable comorbidities without affecting overall survival.Level of Evidence Level III, therapeutic study.

Multi-institutional validation of the ESMO-ESGO-ESTRO consensus conference risk grouping in Turkish endometrial cancer patients treated with comprehensive surgical staging.

In this study, 683 patients with endometrial cancer (EC) after comprehensive surgical staging were classified into four risk groups as low (LR), intermediate (IR), high-intermediate (HIR) and high-risk (HR), according to the recent consensus risk grouping. Patients with disease confined to the uterus, ≥50% myometrial invasion (MI) and/or grade 3 histology were treated with vaginal brachytherapy (VBT). Patients with stage II disease, positive/close surgical margins or extra-uterine extension were treated with external beam radiotherapy (EBRT)±VBT. The median follow-up was 56 months. The overall survival (OS) was significantly different between LR and HR groups, and there was a trend between LR and HIR groups. Relapse-free survival (RFS) was significantly different between LR and HIR, LR and HR and IR and HR groups. There was no significant difference in OS and RFS rates between the HIR and HR groups. In HR patients, the OS and RFS rates were significantly higher in stage IB - grade 3 and stage II compared to stage III and non-endometrioid histology without any difference between the two uterine-confined stages and between stage III and non-endometrioid histology. The current risk grouping does not clearly discriminate the HIR and IR groups. In patients with comprehensive surgical staging, a further risk grouping is needed to distinguish the real HR group.Impact statementWhat is already known on this subject? The standard treatment for endometrial cancer (EC) is surgery and adjuvant radiotherapy (RT) and/or chemotherapy is recommended according to risk factors. The recent European Society for Medical Oncology (ESMO), European Society of Gynaecological Oncology (ESGO) and European Society for Radiotherapy and Oncology (ESTRO) guideline have introduced a new risk group. However, the risk grouping is still quite heterogeneous.What do the results of this study add? This study demonstrated that the current risk grouping recommended by ESMO-ESGO-ESTRO does not clearly discriminate the intermediate risk (IR) and high-intermediate risk (HIR) groups.What are the implications of these findings for clinical practice and/or further research? Based on the results of this study, a new risk grouping can be made to discriminate HIR and IR groups clearly in patients with comprehensive surgical staging.