A Human IgSF Cell-Surface Interactome Reveals a Complex Network of Protein-Protein Interactions.

Cell-surface protein-protein interactions (PPIs) mediate cell-cell communication, recognition, and responses. We executed an interactome screen of 564 human cell-surface and secreted proteins, most of which are immunoglobulin superfamily (IgSF) proteins, using a high-throughput, automated ELISA-based screening platform employing a pooled-protein strategy to test all 318,096 PPI combinations. Screen results, augmented by phylogenetic homology analysis, revealed ∼380 previously unreported PPIs. We validated a subset using surface plasmon resonance and cell binding assays. Observed PPIs reveal a large and complex network of interactions both within and across biological systems. We identified new PPIs for receptors with well-characterized ligands and binding partners for "orphan" receptors. New PPIs include proteins expressed on multiple cell types and involved in diverse processes including immune and nervous system development and function, differentiation/proliferation, metabolism, vascularization, and reproduction. These PPIs provide a resource for further biological investigation into their functional relevance and may offer new therapeutic drug targets.

Vulvar Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget's disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.

NCCN Guidelines® Insights: Cervical Cancer, Version 1.2024.

The NCCN Guidelines for Cervical Cancer provide recommendations for all aspects of management for cervical cancer, including the diagnostic workup, staging, pathology, and treatment. The guidelines also include details on histopathologic classification of cervical cancer regarding diagnostic features, molecular profiles, and clinical outcomes. The treatment landscape of advanced cervical cancer is evolving constantly. These NCCN Guidelines Insights provide a summary of recent updates regarding the systemic therapy recommendations for recurrent or metastatic disease.

Characterizing impact of positive lymph node number in endometrial cancer using machine-learning: A better prognostic indicator than FIGO staging?

BACKGROUND: Number of involved lymph nodes (LNs) is a crucial stratification factor in staging of numerous disease sites, but has not been incorporated for endometrial cancer. We evaluated whether number of involved LNs provide improved prognostic value. PATIENTS AND METHODS: Patients diagnosed with node-positive endometrial adenocarcinoma without distant metastasis were identified in the National Cancer Database. We trained a machine-learning based model of overall survival. Shapley additive explanation values (SHAP) based on the model were used to identify cutoffs of number of LNs involved. Results were validated using a Cox proportional hazards regression model. RESULTS: We identified 11,381 patients with endometrial cancer meeting the inclusion criteria. Using the SHAP values, we selected the following thresholds: 1-3 LNs, 4-5 LNs, and 6+ LNs. The 3-year OS was 82.0% for 1-3 LNs, 74.3% for 4-5 LNs (hazard ratio [HR] 1.38; p < 0.001), and 59.9% for 6+ LNs (HR 2.23; p < 0.001). On univariate Cox regression, PA nodal involvement was a significant predictor of OS (HR 1.20; p < 0.001) but was not significant on multivariate analysis when number of LNs was included (HR 1.05; p = 0.273). Additionally, we identified an interaction between adjuvant therapy and number of involved LNs. Patients with 1-3 involved LNs had 3-year OS of 85.2%, 78.7% and 74.2% with chemoradiation (CRT), chemotherapy, and radiation, respectively. Patients with 6+ involved LNs had 3-yr OS of 67.8%, 49.6%, and 48.9% with CRT, chemotherapy, and radiation, respectively (p < 0.001). CONCLUSION: Number of involved LNs is a stronger prognostic and predictive factor compared to PA node involvement.

Optimal overall treatment time for adjuvant therapy for women with completely resected, node-positive vulvar cancer.

INTRODUCTION: The optimal overall treatment time (OTT) from radical surgery to the end of adjuvant radiation therapy for some squamous cell carcinomas has been found to impact treatment outcomes. This study aims to identify the impact of OTT on overall survival (OS) for women with completely resected, node-positive squamous cell carcinomas of the vulva. MATERIALS AND METHODS: The National Cancer Data Base was queried for women with surgically resected, node-positive vulvar squamous cell carcinomas between 2004 and 2016 who were treated with adjuvant radiation therapy. Kaplan-Meier analysis with log-rank test and Cox proportional hazards tests were utilized for OS calculations. RESULTS: A total of 1500 women met inclusion criteria. The median OTT was 104 days. Shorter OTT was associated with age, facility volume, private insurance, and duration of post-operative hospitalization. Median OS with OTT ≤ 104 days was 56.1 months vs 45.4 months if ≥105 days (p = 0.015). On multivariable Cox analysis, OTT was independently associated with an increased risk of death of 0.4% per additional day (95%CI 1.001-1.007, p = 0.003), as were age at diagnosis (HR 1.031 [95%CI 1.024-1.037], p < 0.001), number of nodes positive (HR 1.031 [95%CI 1.024-1.037], p = 0.006), the use of concurrent chemotherapy (HR 0.815 [95%CI 0.693-0.960], p = 0.014) and increasing pT/pN stage. After propensity adjustment for factors predicting a shorter OTT, OTT continued to be associated with an increased risk of death per additional day (HR 1.004 [95%CI 1.001-1.007], p = 0.007). CONCLUSION: Overall treatment time is an independent risk factor for death in women being treated with adjuvant radiation therapy following complete resection of node-positive squamous cell carcinoma of the vulva.

Dosimetric comparison of multiple vs single isocenter technique for linear accelerator-based stereotactic radiosurgery: The Importance of the six degree couch.

PURPOSE: Single isocenter technique (SIT) for linear accelerator-based stereotactic radiosurgery (SRS) is feasible. However, SIT introduces the potential for rotational error which can lead to geographical miss. Additional planning treatment volume (PTV) margin is required when using SIT. With the six degrees of freedom (6DoF) couch, rotational error can be minimized. We sought to evaluate the effect of the 6DoF couch on the dosimetry of patients with multiple brain metastases treated with SIT. MATERIALS AND METHODS: Ten consecutive patients treated with SRS to ≥3 metastases were identified. Original treatments had MIT plans (MITP). The lesions were replanned using SIT. Lesions 5-10 cm from isocenter had an additional 1mm of margin. Patients were replanned with these additional margins to account for inability to correct rotational error (SITPM). Multiple dosimetric variables and time metrics were evaluated. Dosimetry planning time (DPT) and patient treatment time (PTT) were evaluated. Statistics were calculated using the Wilcoxon signed-rank test. RESULTS: A total of 73 brain metastases receiving SRS, to a median of 6 lesions per patient, were identified. MITPs treated 73 lesions with 63 isocenters. On average, MITPs had a 19.2% higher brain V12 than SITPs (P = 0.017). For creation of SITPM, 30 lesions required 1 mm of additional margin, while none required 2 mm of margin. This increased V12 by 47.8% on average per patient (P = 0.008) from SITP to SITPM. DPT was 5.5 hours for SITP, while median for MITP was 12.5 hours (P = 0.005) PTT was 30 minutes for SITP, while median for MITP was 144 minutes (P = 0.005). CONCLUSIONS: SITPs are comparable to MITPs if rotational error can be corrected with the use of a 6DoF couch. Increasing margin to account for rotational error leads to a nearly 50% increase in V12, which could result in higher rates of radiation necrosis. Time savings are significant using SIT.

Declining brachytherapy utilization for cervical cancer patients - Have we reversed the trend?

OBJECTIVE: Studies examining temporal trends in cervical brachytherapy use are conflicting and examined different health insurance populations. This study examined brachytherapy utilization over time by health insurance type and whether reported declines in brachytherapy have reversed. METHODS: The National Cancer Database (NCDB) was queried for patients with FIGO IIB-IVA cervical cancer treated with definitive chemoradiotherapy between 2004 and 2014, identifying 17,442 patients. Brachytherapy utilization over time and by insurance type and other sociodemographic factors were compared using binary logistic regression. A sensitivity analysis was done in a sub-cohort of patients using the boost modality variable in the NCDB. RESULTS: Brachytherapy utilization declined during 2008-10 (52.6%) compared to 2004-2007 (54.4%; odds ratio [OR] 0.93, 95% confidence interval [CI] 0.86-1.01) and declines were disproportionately larger for patients with government insurance (49.4% vs 52.3%, respectively) than privately-insured patients (57.6% vs 58.9%, respectively). However, rates of brachytherapy use subsequently recovered during 2011-14 in all insurance groups (58.0%, OR 1.24, 95% CI 1.16-1.34) and was especially improved for Medicaid (OR 1.44, 95% CI 1.26-1.65) and uninsured patients (OR 1.28, 95% CI 1.03-1.57). Sensitivity analysis using the boost modality variable confirmed these trends. CONCLUSIONS: In patients with FIGO IIB-IVA cervical cancer treated with definitive chemoradiotherapy from 2004 to 2014, brachytherapy utilization declined during the late 2000s and disproportionately affected patients with government insurance, but subsequently recovered in the early 2010s. Since government insurance covers vulnerable patient populations at-risk for future declines in brachytherapy use, proposed alternative payment models should incentivize cervical brachytherapy to solidify gains in brachytherapy utilization.

External beam radiation and brachytherapy boost at different facilities is associated with increased treatment delays in cervical cancer.

INTRODUCTION: Due to variation in facility expertise and capabilities, patients commonly complete external beam radiation therapy at one facility and brachytherapy boost at another. We evaluated the association of external beam radiation therapy and brachytherapy at the same facility versus different facilities with treatment delays and survival. METHODS: Patients receiving definitive external beam radiation therapy and brachytherapy for non-metastatic cervical cancer from 2004 to 2015 were identified in the National Cancer Database. Treatment delays were classified based on published thresholds: a course of >56 days was considered delayed, >65 days moderately delayed, and >77 days severely delayed. Fisher's exact test and logistic regression were used to evaluate the association of same facility versus different facilities with treatment delays and predictors of same facility versus different facility treatment. RESULTS: We identified 23 911 patients meeting the inclusion criteria at a median follow-up of 39.7 months (IQR 21.0-72.6 months), with 17 391 patients (72.7%) receiving same facility treatment and 6520 patients (27.3%) receiving different facility treatment. Any treatment delay was found in 49.3% of same facility treatments versus 51.9% of different facility treatments (p<0.001); moderate or worse delays in 24.8% of same facility versus 29.4% of different facility treatments (p<0.001); severe treatment delays in 11.3% of same facility versus 15.5% of different facility treatments (p<0.001). Receipt of same facility versus different facility treatment was independently associated with treatment delays (OR 1.28, 95% CI 1.20 to 1.37; p<0.001). Both treatment delays, particularly moderate delays (HR 1.20, 95% CI 1.13 to 1.28; p<0.001) and severe delays (HR 1.32, 95% CI 1.24 to 1.41; p<0.001), and different facility treatments (HR 1.11, 95% CI 1.06 to 1.16; p<0.001) were associated with worse survival. CONCLUSIONS: Delivery of external beam radiation therapy and brachytherapy at different facilities was associated with treatment delays and worse survival. Our findings underscore the importance of care coordination in cervical cancer management.

Race-driven survival differential in women diagnosed with endometrial cancers in the USA.

OBJECTIVE: African American women are increasingly being diagnosed with advanced and type II histology endometrial cancers. Outcomes have been observed to be worse in African American women, but whether or not race itself is a factor is unclear. We sought to evaluate the rates of diagnosis and outcomes on a stage-by-stage basis with respect to race using a large national cancer registry database. METHODS: The National Cancer Data Base was searched for patients with surgically staged non-metastatic endometrial cancer between 2004 and 2015. Women were excluded if surgical stage/histology was unknown, there was no follow-up, or no information on subsequent treatment. Pairwise comparison was used to determine temporal trends and Cox hazards tests with Bonferroni correction were used to determine overall survival. RESULTS: A total of 286 920 women were diagnosed with endometrial cancer and met the criteria for analysis. Median follow-up was 51 months (IQR 25.7-85.3). In multivariable models, in women with stage I disease, African American women had a higher risk of death than Caucasian women (HR 1.262, 95% CI 1.191 to 1.338, p<0.001) and Asian/Pacific Islander women had a lower risk of death than Caucasian women (HR 0.742, 95% CI 0.689 to 0.801, p<0.001). This held for African American women with stage II type I and type II disease (HR 1.26, 95% CI 1.109 to 1.444, p<0.001 and HR 1.235, 95% CI 1.098 to 1.388, p<0.001) but not for Asian/Pacific Islander women. African American women with stage IIIA-B disease also had a higher risk of death for type I and type II disease versus Caucasian women (HR 1.221, 95% CI 1.045 to 1.422, p=0.010 and HR 1.295, 95% CI 1.155 to 1.452, p<0.001). Asian/Pacific Islander women had a lower risk of death than Caucasian women with type I disease (HR 0.783, 95% CI 0.638 to 0.960, p=0.019) and type II disease (HR 0.790, 95% CI 0.624 to 0.999, p=0.05). African American women with stage IIIC1-2 had a higher risk of death with type I disease (HR 1.343, 95% CI 1.207 to 1.494, p<0.001) and type II disease (HR 1.141, 95% CI 1.055 to 1.233, p=0.001) whereas there was no significant difference between Caucasian women and Asian/Pacific Islander women. CONCLUSION: Race appears to play an independent role in survival from endometrial cancer in the USA, with African American women having worse survival on a stage-for-stage basis compared with Caucasian women.

Outcomes after definitive re-irradiation with 3D brachytherapy with or without external beam radiation therapy for vaginal recurrence of endometrial cancer.

BACKGROUND: Limited outcome data exists on salvage re-irradiation for vaginal relapse of previously-irradiated endometrial cancer. We report our 10-year experience with management of vaginal recurrence using definitive intent re-irradiation brachytherapy with or without EBRT. METHODS: A retrospective review was performed on 22 patients treated with definitive-intent re-irradiation brachytherapy ±â€¯EBRT for vaginal recurrence of endometrial cancer. The cumulative rectosigmoid and bladder D2cc (EQD2) were limited to <75 Gy and <90 Gy, respectively. Kaplan-Meier and Cox proportional hazards modeling were used to estimate survival. Severe (grade 3 or higher) radiation-related toxicities, defined according to CTCAE v4, were recorded. RESULTS: Prior radiation therapy consisted of vaginal brachytherapy (54.5%), pelvic EBRT (22.7%), or combination pelvic EBRT and brachytherapy (22.7%). Median re-irradiation interval was 26.6 months. Salvage re-irradiation consisted of EBRT with brachytherapy in 50.0% and brachytherapy alone in 50.0%. Median HR-CTV D90 (EQD2) was 64.5 Gy (IQR: 49.6-75.8). Median cumulative D2cc for bladder, rectum, and sigmoid were 72.1 Gy (range: 30.3-81.8), 70.6 Gy (range: 32.0-80.5), and 52.7 Gy (range: 29.6-75.3), respectively. At a median follow-up of 27.6 months, 3-year local control, regional control, disease-free survival, and overall survival rates were 65.8%, 76.6%, 40.8%, and 68.1%, respectively. There were no grade ≥ 3 acute or late rectosigmoid or bladder toxicities. CONCLUSION: Re-irradiation with 3D conformal brachytherapy for vaginal recurrence is feasible and safe as long as cumulative dose to surrounding normal organs is limited, and offers a chance to potentially salvage 40% of patients presenting with vaginal recurrence in the setting of prior pelvic radiation.

Impact of Surgical Resection on Survival Outcomes After Chemoradiotherapy in Anal Adenocarcinoma.

BACKGROUND: Anal adenocarcinoma is a rare malignancy with a poor prognosis, and no randomized data are available to guide management. Prior retrospective analyses offer differing conclusions on the benefit of surgical resection after chemoradiotherapy (CRT) in these patients. We used the National Cancer Database (NCDB) to analyze survival outcomes in patients undergoing CRT with and without subsequent surgical resection. METHODS: Patients with adenocarcinoma of the anus diagnosed in 2004 through 2015 were identified using the NCDB. Patients with metastatic disease and survival <90 days were excluded. We analyzed patients receiving CRT and stratified by receipt of surgical resection. Logistic regression was used to evaluate predictors of use of surgery and to form a propensity score-matched cohort. Overall survival (OS) was compared between treatment strategies using Cox proportional hazards regression. RESULTS: We identified 1,747 patients with anal adenocarcinoma receiving CRT, of whom 1,005 (58%) received surgery. Predictors of increased receipt of surgery included age <65 years, private insurance, overlapping involvement of the anus and rectum, N0 disease, and external-beam radiation dose ≥4,000 cGy. With a median follow-up of 3.5 years, 5-year OS was 61.1% in patients receiving CRT plus surgery compared with 39.8% in patients receiving CRT alone (log-rank P<.001). In multivariate analysis, surgery was associated with significantly improved OS (hazard ratio, -0.59; 95% CI, 0.50-0.68; P<.001). This survival benefit persisted in a propensity score-matched cohort (log-rank P<.001). CONCLUSIONS: In the largest series of anal adenocarcinoma cases to date, treatment with CRT followed by surgery was associated with a significant survival benefit compared with CRT alone in propensity score-matching analysis. Our findings support national guideline recommendations of neoadjuvant CRT followed by resection for patients with anal adenocarcinoma.

Role of Locoregional Treatment in Vulvar Cancer With Pelvic Lymph Node Metastases: Time to Reconsider FIGO Staging?

BACKGROUND: Vulvar cancer with pelvic nodal involvement is considered metastatic (M1) disease per AJCC staging. The role of definitive therapy and its resulting impact on survival have not been defined. PATIENTS AND METHODS: Patients with pelvic lymph node-positive vulvar cancer diagnosed in 2009 through 2015 were evaluated from the National Cancer Database. Patients with known distant metastatic disease were excluded. Logistic regression was used to evaluate use of surgery and radiation therapy (RT). Overall survival (OS) was evaluated with log-rank test and Cox proportional hazards modeling (multivariate analysis [MVA]). A 2-month conditional landmark analysis was performed. RESULTS: A total of 1,304 women met the inclusion criteria. Median follow-up was 38 months for survivors. Chemotherapy, RT, and surgery were used in 54%, 74%, and 62% of patients, respectively. Surgery was associated with prolonged OS (hazard ratio [HR], 0.58; P<.001) but had multiple significant differences in baseline characteristics compared with nonsurgical patients. In patients managed nonsurgically, RT was associated with prolonged OS (HR, 0.66; P=.019) in MVA. In patients undergoing surgery, RT was associated with better OS (3-year OS, 55% vs 48%; P=.033). Factors predicting use of RT were identified. MVA revealed that RT was associated with prolonged OS (HR, 0.75; P=.004). CONCLUSIONS: In this cohort of women with vulvar cancer and positive pelvic lymph nodes, use of RT was associated with prolonged survival in those who did not undergo surgery. Surgery followed by adjuvant RT was associated with prolonged survival compared with surgery alone.

Early mortality of stage IV non-small cell lung cancer in the United States.

Background: Early mortality is a major deterrent to oncologic management, often preventing delivery of therapy or leading to administration of treatment that offers limited benefit from aggressive interventions. Due to more recent progress in therapeutic options for stage IV non-small cell lung cancer (NSCLC) patients, identifying those at high risk of early mortality (within 30 days) could have implications for treatment selection. Because early mortality following diagnosis of metastatic non-small cell lung cancer (NSCLC) is not well-characterized, this investigation evaluated national trends and predictors thereof. Material and methods: The National Cancer Database was queried for cases of pathologically confirmed metastatic NSCLC with complete vital status and clinical information, diagnosed between 2006 and 2014. Multivariable logistic regression ascertained factors associated with 30-day mortality. Results: Of 346,681 patients, 45,861 (13%) experienced early mortality over the past decade, which remained relatively constant over time. Predictors of early mortality included advancing age (>65 years), male gender, Caucasian race, non-private insurance, lower income, greater comorbidities, residence in metropolitan and/or lesser-educated areas, treatment at community centers, patients with no prior history of cancer and regional differences (p < .01 for all). Early mortality was highest in patients older than 80 years with multiple comorbidities (29%). The majority of patients (71%) who died within 30 days did not receive any therapy. Conclusions: A fair proportion of NSCLC patients experience early mortality, which has not decreased over time. The majority of patients with early mortality do not receive treatment. Prognostic factors for early mortality should be considered during initial evaluation and subsequent follow-up of these patients. Doing so may impact systemic treatment selection by medical oncologists, management of (oligo)metastatic disease by radiation and surgical oncologists and cost-effective administration of these therapies in the stage IV NSCLC population.

A proposal for a new classification of "unfavorable risk criteria" in patients with stage I endometrial cancer.

BACKGROUND: Randomized trials describe differing sets of high-intermediate risk criteria. OBJECTIVE: To use the National Cancer Database to compare the impact of radiation therapy in patients with stage I endometrial cancer meeting different criteria, and define a classification of "unfavorable risk." METHODS: Patients with stage I endometrial cancer between January 2010 and December 2014 were identified in the National Cancer Database and stratified into two cohorts: (1) patients meeting Gynecologic Oncology Group (GOG)-99 criteria only for high-intermediate risk, but not Post-Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-1 criteria and (2) those meeting PORTEC-1 criteria only. High-risk stage I patients with both FIGO stage IB (under FIGO 2009 staging) and grade 3 disease were excluded. In each cohort, propensity score-matched survival analyses were performed. Based on these analyses, we propose a new classification of unfavorable risk. We then analyzed the association of adjuvant radiation with survival, stratified by this classification. RESULTS: We identified 117,272 patients with stage I endometrial cancer. Of these, 11,207 patients met GOG-99 criteria only and 5,920 patients met PORTEC-1 criteria only. After propensity score matching, adjuvant radiation therapy improved survival (HR=0.73; 95% CI 0.60 to 0.89; p=0.002) in the GOG-99 only cohort. However, there was no benefit of adjuvant radiation (HR=0.89; 95% CI 0.69 to 1.14; p=0.355) in the PORTEC-1 only cohort. We, therefore, defined unfavorable risk stage I endometrial cancer as two or more of the following risk factors: lymphovascular invasion, age ≥70, grade 2-3 disease, and FIGO stage IB. Adjuvant radiation improved survival in stage I patients with adverse risk factors (HR=0.74; 95% CI 0.68 to 0.80; p<0.001), but not in other stage I patients (HR=1.02; 95% CI 0.91 to 1.15; p=0.710; p interaction <0.001). CONCLUSION: Our study showed that adjuvant radiation was associated with an overall survival benefit in patients meeting GOG-99 criteria only; however, no survival benefit was seen in patients meeting PORTEC-1 criteria only. We propose a definition of unfavorable risk stage I endometrial cancer: ≥2 risk factors from among lymphovascular invasion, age ≥70, grade 2-3 disease, and FIGO stage IB disease.

Improved survival with adjuvant brachytherapy in stage IA endometrial cancer of unfavorable histology.

PURPOSE: We evaluated the utilization of vaginal brachytherapy (BT) and the resulting impact on survival in stage IA endometrial cancer of clear cell (CC), papillary serous (PS), and carcinosarcoma (CS) histology. METHODS: Patients with uterine cancer diagnosed from 2004 to 2015 were identified from the National Cancer Database. Patients underwent hysterectomy, showing FIGO stage IA disease with CC, PS, or CS histology. Logistic regression was used to evaluate predictors of BT utilization and to generate propensity scores. Survival was compared using log-rank test and Cox proportional hazards modeling, with propensity score adjustment. RESULTS: We identified 5711 patients who underwent hysterectomy showing FIGO pT1a, N0 or NX endometrial cancer with CC, PS, or CS histology, of which 29.5% received BT. Multivariate predictors of increased receipt of BT were identified. With a median follow-up of 3.3 years, 3-year overall survival (OS) was 87% for those receiving BT versus 78% for those without (p < 0.001). A survival benefit to BT was maintained across histologies. Similar results were seen whether tumor was confined to endometrium or had <50% myometrial invasion. On multivariate analysis, receipt of BT was associated with increased survival (hazard ratio [HR] 0.75, 95% confidence interval 0.65-0.87, p < 0.001). The benefit of BT persisted after propensity score adjustment (HR 0.76, p < 0.001). CONCLUSIONS: In this cohort of women with stage IA endometrial cancer of unfavorable histology, the use of BT was associated with improved survival. In this study, 29.5% of patients in our cohort received BT.

Image-based multichannel vaginal cylinder brachytherapy for the definitive treatment of gynecologic malignancies in the vagina.

PURPOSE: Brachytherapy is integral to vaginal cancer treatment and is typically delivered using an intracavitary single-channel vaginal cylinder (SCVC) or an interstitial brachytherapy (ISBT) applicator. Multi-channel vaginal cylinder (MCVC) applicators allow for improved organ-at-risk (OAR) sparing compared to SCVC while maintaining target coverage. We present clinical outcomes of patients treated with image-based high dose-rate (HDR) brachytherapy using a MCVC. METHODS AND MATERIALS: Sixty patients with vaginal cancer (27% primary vaginal and 73% recurrence from other primaries) were treated with combination external beam radiotherapy (EBRT) and image-based HDR brachytherapy utilizing a MCVC if residual disease thickness was 7 mm or less after EBRT. All pts received 3D image-based BT to a total equivalent dose of 70-80 Gy. RESULTS: The median high-risk clinical target volume was 24.4 cm3 (interquartile range [IQR], 14.1), with a median dose to 90% of 77.2 Gy (IQR, 2.8). After a median follow-up of 45 months (range, 11-78), the 4-year local-regional control, distant control, DFS, and OS rates were 92.6%, 76.1%, 64.0%, and 67.2%, respectively. The 4-year LRC rates were similar between the primary vaginal (92%) and recurrent (93%) groups (p = 0.290). Pts with lymph node positive disease had a lower rate of distant control at 4 years (22.7% vs. 89.0%, p < 0.001). There were no Grade 3 or higher acute complications. The 4-year rate of late Grade 3 or higher toxicity was 2.7%. CONCLUSIONS: Clinical outcomes of pts with primary and recurrent vaginal cancer treated definitively in a systematic manner with combination EBRT with image-guided HDR BT utilizing a MCVC applicator demonstrate high rates of local control and low rates of severe morbidity. The MCVC technique allows interstitial implantation to be avoided in select pts with ≤7 mm residual disease thickness following EBRT while maintaining excellent clinical outcomes with extended 4-year follow-up in this rare malignancy.

Chemoradiation Improves Survival Compared With Chemotherapy Alone in Unresected Nonmetastatic Gastric Cancer.

Background: Limited data are available to guide management of patients with stage I-III gastric cancer not undergoing potentially curative surgical resection. We compared survival outcomes associated with chemotherapy alone versus chemoradiation (CRT) in the treatment of nonmetastatic gastric cancer. Methods: Patients with gastric adenocarcinoma from 2004 to 2015 were identified using the National Cancer Database. Patients were excluded if they had surgery, metastatic disease, or T0, Tis, or T1a disease. Logistic regression was used to evaluate predictors of CRT use. Cox proportional hazards modeling was performed to compare overall survival (OS) between chemotherapy alone and CRT in overall and propensity score-matched cohorts. Results: We identified 4,795 patients with stage I-III gastric adenocarcinoma who did not undergo surgery, at a median follow-up of 11.8 months. A total of 3,316 patients (69.2%) received chemotherapy alone and 1,479 patients (30.8%) received CRT. Predictors of increased CRT use were age ≥65 years (odds ratio [OR] 1.68; 95% CI, 1.43-1.99; P<.001), Charlson-Deyo comorbidity score ≥2 (OR, 1.46; 95% CI, 1.18-1.81), and treatment at a community facility (OR, 1.27; 95% CI, 1.07-1.51; P=.006). Patients receiving CRT had a 2-year OS rate of 28.3% compared with 21.5% among those receiving chemotherapy. Multivariate analysis showed that CRT was associated with improved OS (hazard ratio [HR], 0.82; 95% CI, 0.77-0.89; P<.001). After propensity score matching, a persistent survival benefit was observed (HR, 0.80; 95% CI, 0.74-0.88; P<.001). Conclusions: In patients with stage I-III gastric cancer not undergoing surgical resection, CRT was associated with improved survival compared with chemotherapy alone. However, only 30.8% of patients received CRT in this setting.

Rising Rates of Upfront Surgery in Early Locally Advanced Cervical Cancer: What Factors Predict for This Treatment Paradigm?

OBJECTIVE: In this study, we analyzed patterns of care for patients with locally advanced cervical cancer to identify predictors for upfront surgery compared with definitive chemoradiation (CRT). METHODS: The National Cancer Database was queried for patients aged 18 years or older with Federation of Gynecology and Obstetrics IB2-IIB cervical cancer. All patients underwent either upfront hysterectomy with or without postoperative radiation therapy versus definitive CRT. Logistic regression was used to assess variables associated with modality of treatment (surgery vs CRT). RESULTS: Of the 9494 patients included, 2151 (22.7%) underwent upfront surgery. Of those undergoing surgery, 380 (17.7%) had positive margins, 478 (22.2%) had positive nodes, and 458 (21.3%) had pathologic involvement of the parametrium. Under multiple logistic regression, rates of surgery significantly increased from 2004 (12.2%) to 2012 (31.2%) (odds ratio [OR] per year increase, 1.15; confidence interval [CI], 1.12-1.17; P < 0.001). Upfront surgery was more commonly performed in urban (OR, 1.21; 95% CI, 1.03-1.41; P = 0.018) and rural counties (OR, 1.79; 95% CI, 1.24-2.58; P = 0.002), for adenocarcinoma (OR, 2.14; 1.88-2.44; P < 0.001) and adenosquamous (OR, 2.69; 2.11-3.43; P < 0.001) histologies, and in patients from higher median income communities (ORs, 1.19-1.37). Upfront surgery was less common at academic centers (OR, 0.73; 95% CI, 0.58-0.93; P = 0.011). CONCLUSIONS: Rates of upfront surgery relative to definitive CRT have increased significantly over the past decade. In the setting of level 1 evidence supporting the use of definitive CRT alone for these women, the rising rates of upfront surgery raises concern for both unnecessary surgical procedures with higher rates of treatment-related morbidity and greater health care costs.

The impact of the omission or inadequate dosing of radiotherapy in extranodal natural killer T-cell lymphoma, nasal type, in the United States.

BACKGROUND: Extranodal natural killer T-cell lymphoma, nasal-type (NKTCL), is a rare malignancy in Western populations and is thus challenging for standardization of care and a prospective study. This study was aimed at defining patterns of care for NKTCL in the context of radiotherapy (RT) use and dose selection in the United States. METHODS: Six hundred forty-two stage I-II NKTCL patients from 1998 to 2012 were identified from the National Cancer Data Base. Binary logistic regression analyses were performed to identify sociodemographic, treatment, and tumor characteristics predictive of the treatment selection and RT dose. Overall survival (OS) analyses were completed with the Kaplan-Meier and Cox multivariate methods, including a propensity score adjustment for a potential indication bias. RESULTS: Of the 642 included NKTCL patients, 70% were at stage I, 79% were white, and 66% were ≤ 60 years old. Fifty-five percent received chemotherapy plus RT, 19% received RT alone, and 27% received chemotherapy alone. The median RT dose was 50 Gy (interquartile range, 43.2-54 Gy), 37% received < 45 Gy, and 43% received < 50 Gy. A multivariate survival analysis showed improved OS in comparison with chemotherapy alone for RT alone at ≥50 Gy (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.23-0.70; P < .01), for chemotherapy plus RT at <50 Gy (HR, 0.55, 95% CI, 0.36-0.86; P < .01), and for chemotherapy plus RT at ≥50 Gy (HR, 0.41; 95% CI, 0.27-0.63; P < .01). CONCLUSIONS: Stage I-II NKTCL patients in the United States commonly receive chemotherapy alone or suboptimal-dose RT. The omission of RT or the use of suboptimal RT is negatively associated with OS. Efforts to continue improving evidenced-based management are warranted. Cancer 2017;123:3176-85. © 2017 American Cancer Society.

Image-guided tandem and cylinder brachytherapy as monotherapy for definitive treatment of inoperable endometrial carcinoma.

OBJECTIVES: Management of endometrial cancer consists of surgical staging with adjuvant therapy guided by risk factors, though some women cannot undergo surgery due to comorbidities. We present a series of women treated with definitive high-dose rate image-guided tandem and cylinder brachytherapy (HDR-IGBT) alone. METHODS: Patients with grade 1-2, clinical stage I endometrial adenocarcinoma, <50% myometrial invasion, and tumor≤2cm were reviewed. Definitive treatment consisted of 5-6 fractions HDR-IGBT alone with CT- or MRI-based planning. Local-regional control (LRC) was defined as complete imaging response and/or cessation of vaginal bleeding. RESULTS: From 2007 to 2016, 45 patients were treated to a median dose of 37.5Gy. The median gross tumor volume (GTV) and clinical target volume (CTV) were 5.9cm3 (range, 0.7-18.7) and 80.9cm3 (17.2-159.0), respectively. The median cumulative dose to 90% (D90) of the GTV was 132.8Gy (76.5-295.6) equivalent 2Gy dose, and the median CTV D90 was 49.7Gy (34.5-57.2). Median follow-up among living patients was 18.6months (3.0-64.3). Cessation of vaginal bleeding occurred in 98%. Among those with post-treatment MRI (64%), complete radiographic response was demonstrated in 90%. The 2-year LRC, cancer-specific survival, and overall survival rates were 90%, 86%, and 97%, respectively. No grade 3+ acute or late toxicity was observed. CONCLUSIONS: HDR-IGBT alone for treatment of early-stage, medically inoperable endometrial cancer is feasible with excellent response rates and clinical results. This approach also allows sparing of critical organs and ensures target coverage, which contributed to the low toxicity rate and high LRC in comparison with 2D point-based series.