Refusal of surgery and survival outcomes in endometrial cancer.

OBJECTIVES: The goal of this study was to determine the impact refusal of surgery has on overall survival in patients with endometrial cancer. METHODS: From January 2004 to December 2015, the National Cancer Database was queried for patients with pathologically proven endometrial cancer who were recommended surgery and refused. Inverse probability of treatment weighting was used to account for differences in baseline characteristics between patients who underwent surgery and those who refused. Kaplan-Meier analyses and doubly robust estimation with multivariate Cox proportional hazards modeling were used to analyze overall survival. RESULTS: Of the 300 675 patients identified, 534 patients (0.2%) were recommended surgical treatment but refused: 18% (95/534) were age ≤40 years. The 5-year overall survival for all patients who refused surgery was significantly decreased compared with patients who underwent surgery (29.2% vs 71.9%, P<0.01). This was demonstrated at ages 41-64 years (65.5% vs 91.0%, P<0.01) and ≥65 years (23.4% vs 75.3%, P<0.01). The 5-year overall survival did not meet statistical significance at age ≤40 years (90.1% vs 87.8% P<0.19). However, there were few patients in this cohort. On multivariate analysis, factors associated with refusal of surgery included: Medicaid insurance, Black race, Hispanic Race, Charlson Comorbidity Index scores of 2 or greater, stage II or III, and if patient received external beam radiation therapy alone. Factors associated with undergoing surgery included: age greater than 41, stage IB, and if the patient received brachytherapy. CONCLUSIONS: Refusal of surgery for endometrial cancer is uncommon and leads to decreased overall survival.

Recurrent early stage endometrial cancer: Patterns of recurrence and results of salvage therapy.

OBJECTIVE: To analyze our institutional experience and oncologic outcomes for salvage treatment for the recurrence of early-stage endometrial cancer patients. METHODS: We included women of all ages diagnosed with FIGO stage I-II, any grade endometrial cancer from 2000 to 2016 at our institutions who were treated with at least a hysterectomy. Recurrences in the pelvis and/or vagina were considered locoregional recurrences (LRR). Overall survival (OS) was assessed using Kaplan-Meier survival analysis. Univariate (UV) and multivariate (MV) Cox proportional hazards modeling was also used. RESULTS: A total of 2691 women were analyzed. The majority had endometrioid histology (91%), stage IA disease (61%), and were grade 1 (57%). With a median follow-up of 6.1 years, the overall rate of recurrence was 7.2%, and the rate of LRR was 3.7%. Women with vaginal-only recurrences had a longer median OS after recurrence (14.0 years) compared to both pelvic (1.2 years) and distant (1.0 year) failures. For women with vaginal-only recurrences, salvage radiotherapy (RT) was the only factor associated with improved OS on MVA (HR 0.1, p = .04). For women with pelvic recurrences, salvage surgery (HR 0.3, p = .01), salvage RT (HR 0.3, p < .01), and salvage chemotherapy (HR 0.4, p = .03) were associated with improved OS. CONCLUSIONS: Failure rates for women with early-stage endometrial cancer are low. Women with vaginal-only recurrences have improved OS compared to pelvic or distant recurrences. Salvage RT appears to be an important factor for treatment of women with vaginal-only recurrences. Aggressive multimodality treatment may be beneficial for women with pelvic recurrences.

Self-expanding stent effects on radiation dosimetry in esophageal cancer.

It is the purpose of this study to evaluate how self-expanding stents (SESs) affect esophageal cancer radiation planning target volumes (PTVs) and dose delivered to surrounding organs at risk (OARs). Ten patients were evaluated, for whom a SES was placed before radiation. A computed tomography (CT) scan obtained before stent placement was fused to the post-stent CT simulation scan. Three methods were used to represent pre-stent PTVs: 1) image fusion (IF), 2) volume approximation (VA), and 3) diameter approximation (DA). PTVs and OARs were contoured per RTOG 1010 protocol using Eclipse Treatment Planning software. Post-stent dosimetry for each patient was compared to approximated pre-stent dosimetry. For each of the three pre-stent approximations (IF, VA, and DA), the mean lung and liver doses and the estimated percentages of lung volumes receiving 5 Gy, 10 Gy, 20 Gy, and 30 Gy, and heart volumes receiving 40 Gy were significantly lower (p-values < 0.02) than those estimated in the post-stent treatment plans. The lung V5, lung V10, and heart V40 constraints were achieved more often using our pre-stent approximations. Esophageal SES placement increases the dose delivered to the lungs, heart, and liver. This may have clinical importance, especially when the dose-volume constraints are near the recommended thresholds, as was the case for lung V5, lung V10, and heart V40. While stents have established benefits for treating patients with significant dysphagia, physicians considering stent placement and radiation therapy must realize the effects stents can have on the dosimetry.

Refusal of Radiation Results in Inferior Survival in Endometrial Cancer.

OBJECTIVE: We sought to understand factors associated with refusal of adjuvant radiotherapy in endometrial cancer and its impact on outcomes. METHODS: Data from the National Cancer Database for patients who underwent surgery for nonmetastatic endometrial cancer between 2004 and 2015 were pooled. The Pearson χ test and multivariate logistic regression analyses were used to assess demographic, clinical, and treatment factors. Inverse probability of treatment weighting was used to account for differences in baseline characteristics. Kaplan-Meier analyses and doubly-robust estimation with multivariate Cox proportional hazards modeling were used to analyze overall survival (OS). RESULTS: We identified 4739 of 80,803 patients (5.9%) who refused radiotherapy. Factors associated with refusal were: no insurance (relative risk [RR]=1.66, P<0.01), Medicare (RR=1.42, P<0.01), living >50 miles from treatment (RR=1.34, P<0.01), Charlson-Deyo Comorbidity Scores of 1 (RR=1.16, P<0.01) or ≥2 RR=1.38, P<0.01), age above 60 years (RR=1.28, P<0.01), International Federation of Gynecology and Obstetrics (FIGO) stages IIIA (RR=1.63, P<0.01) and IIIC (RR=1.65, P<0.01) disease, papillary (RR=1.69, P<0.01) and clear cell histology (RR=1.64, P<0.01). Factors associated with radiation therapy receipt included: Hispanic race (RR=0.61, P<0.01), income >$63,000 (RR=0.89, P=0.044), undergoing chemotherapy (RR=0.17, P<0.01), FIGO stages IB (RR=0.81, P<0.01) and II (RR=0.70, P<0.01) disease, and lymphadenectomy (RR=0.79, P<0.01). After weighting, 5-year OS was significantly lower with refusal (74.3% vs. 79.7%, P<0.01). This survival decrement was maintained across FIGO stages. CONCLUSIONS: We identified characteristics associated with radiation refusal, including socioeconomic barriers, advanced disease stage, and histology. Refusal of radiotherapy conferred decreased OS across FIGO stages.

The impact of squamous cell carcinoma histology on outcomes in nonmetastatic pancreatic cancer.

BACKGROUND: The prognosis for nonmetastatic, primary pancreatic squamous cell carcinoma (SCC) is thought to be poor compared with adenocarcinoma (AC); however, this is based on limited data. Additionally, the optimal definitive treatment strategy for nonmetastatic pancreatic SCC is unknown. METHODS: We analyzed patients with nonmetastatic pancreatic cancer using the National Cancer Database for patients diagnosed from 2006 to 2014. Patients were analyzed according to histology-only AC, adenosquamous carcinoma (A-SCC), and SCC were included. The primary endpoint was overall survival (OS) from the time of diagnosis. RESULTS: A total of 94 928 cases were included; 94 016 AC, 757 A-SCC, and 155 SCC. Median OS was lower for SCC (8.67 months), compared to AC (13.93 months) and A-SCC (12.71 months, P < .001). SCC was resected less often (25.5% vs 46.7% and 74.5%). On subgroup analysis of patients with pancreatic SCC, factors on multivariate analysis associated with improved survival included surgery (HR 0.19, P < .001), and chemotherapy (HR 0.22, P = .01). In 38 patients with SCC undergoing surgical resection, median OS improved (MS = 6.8 months without surgery vs 21.3 months with surgery, P < .001). CONCLUSIONS: Nonmetastatic pancreatic SCC presents with more advanced disease, which is less often surgically resected or treated with any definitive local therapy. In contrast, AC and A-SCC behave more similarly and have higher surgical resection rates and improved survival. In patients with nonmetastatic SCC of the pancreas, surgical resection provides the most significant survival benefit, with systemic chemotherapy providing a less significant benefit, and localized radiation providing no statistical benefit for any subgroup.

Impact of Brachytherapy Boost and Dose-escalated External Beam Radiotherapy in Margin Positive Cervical Cancer Treated With Chemotherapy and Radiation.

OBJECTIVES: We examined the impact of brachytherapy boost (BB) and external beam radiotherapy (EBRT) dose-escalation on overall survival (OS) for women with cervical cancer receiving postoperative chemotherapy and radiation (CRT) for a positive margin following hysterectomy. MATERIALS AND METHODS: The National Cancer Database (NCDB) was queried from 2004 to 2015 for women with nonmetastatic squamous cell carcinoma or adenocarcinoma of the cervix who had a positive margin following hysterectomy and received postoperative CRT. Patient and treatment characteristics were assessed with multivariate logistic regression. Survival analyses were performed with univariate Cox regression and Kaplan-Meier analyses. Propensity-score weighted cohorts were generated with inverse probability of treatment weighting via generalized boosted regression modeling. RESULTS: Of 630 women receiving CRT, 331 (53%) received EBRT alone and 299 (47%) received EBRT+BB. Eighty-two percent had chemotherapy initiation within 2 weeks of radiation, suggesting concurrent delivery. Median EBRT dose was 5040 cGy. Intracavitary high-dose rate was the most common BB (67%). Inclusion of BB was more likely with larger tumor sizes (odds ratio=1.03, P=0.002). Women receiving EBRT+BB had improved OS compared to EBRT alone for both unweighted (hazard ratio [HR], 0.72; P=0.020) and propensity-score weighted cohorts (HR, 0.70; P=0.017), and this finding was consistent across multiple patient subsets. EBRT dose-escalation >5040 cGy was not found to be associated with OS (unweighted HR, 1.38; P=0.065 and weighted HR, 1.16; P=0.450). CONCLUSION: The addition of BB to standard CRT improved OS for women with cervical cancer and a positive margin after hysterectomy. No consistent survival benefit was seen to EBRT dose-escalation beyond 5040 cGy.

Lymphovascular Invasion in Endometrial Cancer: Prognostic Value and Implications on Adjuvant Radiation Therapy Use.

OBJECTIVES: Lymphovascular space invasion (LVSI) is a known prognostic factor for endometrial carcinomas. However, LVSI as a determinant of treatment benefit has not been fully elucidated. METHODS AND MATERIALS: Data from the National Cancer Database for endometrial cancer from 2004 to 2012 was obtained. Univariate and multivariate analysis was performed to assess the impact of LVSI on overall survival (OS). Survival analysis was performed utilizing log-rank and Kaplan-Meier analyses. The difference in OS between external beam radiation therapy (EBRT) and vaginal brachytherapy (VBT) in LVSI-positive patients was analyzed with propensity score matching. RESULTS: A total of 32,150 patients with surgical stage I to III endometrial carcinomas were available for analysis with a median follow-up of 30 months. Twenty-nine percent were LVSI positive and received adjuvant radiotherapy (aRT) more often than if LVSI negative (57% vs. 37%). On multivariate analysis, LVSI (hazard ratio, 1.94; P<0.01) was associated with an increased risk of death. aRT improved OS for LVSI-negative patients (87% without aRT, 90% with aRT; P=0.006). aRT was particularly effective in LVSI-positive patients: all stages of LVSI-positive patients were associated with an OS benefit (P<0.01), whereas among LVSI-negative patients, only stage III benefited from aRT (P<0.01). After propensity score match, there was no OS difference between EBRT and VBT among LVSI-positive patients (hazard ratio, 1.15; P=0.44). CONCLUSIONS: LVSI is an independent prognostic factor in locoregional endometrial carcinomas. aRT benefited all stages of LVSI-positive patients, but only stage III of LVSI-negative patients. Among LVSI-positive patients, we did not find an OS difference between adjuvant EBRT versus VBT.

Do vaginal recurrence rates differ among adjuvant vaginal brachytherapy regimens in early-stage endometrial cancer?

PURPOSE: We sought to retrospectively examine clinical outcomes for three adjuvant vaginal high-dose-rate (HDR) brachytherapy regimens after hysterectomy for early-stage endometrial cancer. METHODS: Included were women of all ages from two independent hospital systems diagnosed with Stage I-II endometrial cancer of any grade between 2000 and 2016 who underwent hysterectomy followed by adjuvant vaginal cylinder HDR brachytherapy with either 7.0 Gy × 3 fractions prescribed to 0.5 cm vaginal depth, 6.5 Gy × 3 fractions prescribed to 0.5 cm vaginal depth, or 6.0 Gy × 5 fractions prescribed to the vaginal surface. Outcomes included vaginal recurrence (VR), pelvic recurrence, distant recurrence, locoregional recurrence, recurrence-free survival, and overall survival. RESULTS: Of the 348 women, 45 (13%) received 7.0 Gy × 3 fractions, 259 (74%) received 6.5 Gy × 3 fractions, and 44 (13%) received 6.0 Gy × 5 fractions. Women receiving 5-fraction brachytherapy were more likely to be younger with a higher performance status. At a median follow-up of 4.5 years, VR rates were 2.2%, 0.8%, and 4.5%, respectively. Multivariate analysis revealed no significant differences in the risks for VR among brachytherapy regimens. Risks for VR, pelvic recurrence, distant recurrence, locoregional recurrence, recurrence-free survival, and overall survival did not differ between propensity score-matched five- and 3-fraction brachytherapy cohorts. CONCLUSIONS: VR rates after hysterectomy and adjuvant vaginal brachytherapy for early-stage endometrial cancer were low and not significantly different by HDR dose fractionation.

Lymph Node Ratio in Pancreatic Adenocarcinoma After Preoperative Chemotherapy vs. Preoperative Chemoradiation and Its Utility in Decisions About Postoperative Chemotherapy.

BACKGROUND: Single-center studies in pancreatic adenocarcinoma have suggested that preoperative chemotherapy (PCT) is associated with higher lymph node ratio (LNR) than preoperative chemoradiation (PCRT). The association of postoperative chemotherapy with overall survival (OS) in patients treated with PCT and PCRT remains unclear. Our objectives were to investigate whether (1) PCT is associated with higher LNR than PCRT and (2) postoperative chemotherapy is associated with longer OS after PCT and PCRT in LNR-stratified cohorts. METHODS: A retrospective cohort study was performed of patients with pancreatic adenocarcinoma treated with PCT or PCRT followed by resection between 2006 and 2014 in the National Cancer Database. Temporal trends were evaluated with Cuzick's test. OS was evaluated with multivariable Cox regression and inverse probability weighted (IPW) Cox regression. RESULTS: Of 4187 patients, 1993 (47.6%) received PCT. PCT rates were stable at approximately 30% in 2006-2010 (p = 0.33) but increased to 64.9% by 2014 (p < 0.001). Node positivity rates were higher after PCT than PCRT (62.7 vs. 41.8%, P < 0.001) and mean LNR was higher (0.10 [95% CI 0.096, 0.11] vs. 0.058 [95% CI 0.052, 0.063], P < 0.001). Postoperative chemotherapy was associated with longer OS in patients with LNR 0.01-0.149 after PCT by univariate analysis (median OS 34.5 vs. 26.5 months, P = 0.002), multivariable Cox regression (HR 0.64, 95% CI 0.48, 0.84), and IPW Cox regression (HR 0.72, 95% CI 0.55, 0.94). Postoperative chemotherapy was not associated with longer OS for patients who were node-negative or who had LNR ≥ 0.15 after PCT or for any patient subgroups after PCRT. CONCLUSIONS: PCT is associated with a higher LNR and higher rates of node positivity than PCRT. Postoperative chemotherapy is associated with longer OS than observation in patients with a LNR of 0.01-0.149 after PCT.

Sequencing of Postoperative Radiotherapy and Chemotherapy for Locally Advanced or Incompletely Resected Non-Small-Cell Lung Cancer.

Purpose Although several feasibility studies have demonstrated the safety of adjuvant concurrent chemoradiotherapy (CRT) for locally advanced or incompletely resected non-small-cell lung cancer (NSCLC), it remains uncertain whether this approach is superior to sequential chemotherapy followed by postoperative radiotherapy (C→PORT). We sought to determine the most effective treatment sequence. Patients and Methods Using the National Cancer Database, we selected two cohorts of patients with nonmetastatic NSCLC who had received at least a lobectomy followed by multiagent chemotherapy and radiotherapy; cohort one included patients with R0 resection and pN2 disease, whereas cohort two included patients with R1-2 resection regardless of nodal status. Overall survival (OS) was examined using a propensity score-matched analysis with a shared frailty Cox regression. Results A total of 747 patients in cohort one and 277 patients in cohort two were included, with a median follow-up of 32.8 and 27.9 months, respectively. The median OS was 58.8 months for patients who received C→PORT versus 40.4 months for patients who received CRT in cohort one (log-rank P < .001). For cohort two, the median OS was 42.6 months for patients who received C→PORT versus 38.5 months for patients who received CRT (log-rank P = .42). After propensity score matching, C→PORT remained associated with improved OS compared with CRT in cohort one (hazard ratio, 1.35; P = .019), and there was no statistical difference in OS between the sequencing groups for cohort two (hazard ratio, 1.35; P = .19). Conclusion Patients with NSCLC who undergo R0 resection and are found to have pN2 disease have improved outcomes when adjuvant chemotherapy is administered before, rather than concurrently with, radiotherapy. For patients with positive margins after surgery, there is not a clear association between treatment sequencing and survival.

Benefit of adjuvant chemotherapy based on lymph node involvement for oesophageal cancer following trimodality therapy.

BACKGROUND: Oesophageal cancer (OC) survival rates have improved since the widespread adoption of neoadjuvant chemoradiation therapy (NACRT) followed by oesophagectomy (trimodality therapy). Unfortunately, the overall prognosis for patients with locally advanced disease remains poor. In this study, we sought to assess the effect of adjuvant chemotherapy (AC) in patients treated with trimodality therapy. METHODS: Using the National Cancer Database we retrospectively identified 6785 patients with locally advanced (cT1b-T4a, N0-N+, M0) OC who were treated with trimodality therapy from 2006 to 2014. Patients were separated based on receipt of AC (n=463), as well as clinical and pathological lymph node involvement. Overall survival (OS) between groups was compared using the Kaplan-Meier method and Cox proportional hazard modelling. RESULTS: Based on multivariate analysis, AC was associated with a statistically significantly reduced risk of death (HR 0.77, p<0.001). Subgroup analysis revealed that AC was associated with reduced risk of death compared with NACRT alone in the cN+/pN0 (median OS 64 vs 43 months; p=0.019) and the cN+/pN+ (median OS 27 vs 22 months; p=0.010) groups, but not in the cN0/pN0 (median OS 48 vs 49 months; p=0.253) or cN0/pN+ (median OS 31 vs 24 months; p=0.077) groups. CONCLUSION: AC following trimodality therapy may improve survival in patients with locally advanced OC. Patients who undergo lymph node downstaging may be the most likely to benefit from AC. Prospective studies are needed to confirm this finding.

Toxicity and Outcomes in Patients With and Without Esophageal Stents in Locally Advanced Esophageal Cancer.

PURPOSE: Esophageal stenting is often considered to relieve dysphagia in patients with locoregionally advanced esophageal cancer. We sought to determine the effects of stenting on the incidence of acute toxicity and oncologic outcomes in patients undergoing chemoradiation therapy (CRT). METHODS AND MATERIALS: The data from patients treated with curative intent CRT for locoregionally advanced esophageal cancer at the University of Utah were retrospectively analyzed. The χ2 or Fisher exact test was used to compare the demographic and tumor characteristics between patients with and without esophageal stenting before RT. Univariate and multivariate analyses using logistic regression modeling were used to identify the predictors of acute toxicities. A propensity score-matched analysis with shared frailty Cox hazard regression was performed according to stent status to identify the stent effect on survival. Acute toxicities were graded using the Common Terminology Criteria for Adverse Events, version 4. RESULTS: From 2005 to 2013, 103 consecutive patients received CRT. Of the 103 patients, 28 had a stent in place during CRT. The median dose was 50.4 Gy for all patients. Grade ≥3 acute toxicities were seen in 71% of the stent versus 27% of the no-stent patients (P<.01), including esophagitis (39% vs 20%; P=.05), dehydration (29% vs 13%; P=.07), and anorexia (14% vs 5%; P=.13). Of the 103 patients, 29% of the stent and 51% of the no-stent patients underwent esophagectomy (P=.05). The only significant predictor for acute toxicity on multivariate analysis was esophageal stenting (odds ratio 8.1; P<.01). After propensity score matching, the stent patients had a worse median overall survival compared with the no-stent patients (11.5 vs 22.0 months; hazard ratio 2.3; P=.016). CONCLUSIONS: In patients undergoing CRT with curative intent, esophageal stenting was associated with significantly increased grade ≥3 acute toxicities, fewer patients proceeding to esophagectomy, and worse overall survival.

Outcomes and utilization of postmastectomy radiotherapy for T3N0 breast cancers.

BACKGROUND: The role of postmastectomy radiotherapy (PMRT) for women with pT3N0M0 breast cancer is controversial. We sought to determine the benefit of PMRT in this cohort using the National Cancer Database (NCDB). METHODS: We analyzed women with pT3N0M0 breast cancer who received mastectomy with or without PMRT between 2004 and 2012. We excluded men, women ≤18 years, neoadjuvant or unknown radiation or chemotherapy status, unknown estrogen or progesterone receptor status, unknown surgical margin status, histology other than invasive ductal or lobular carcinoma, and if death occurred <3 months after diagnosis. A total of 4291 patients was included for analysis. Chi-squared analysis was used to compare patient characteristics. Univariate (UVA) and multivariate (MVA) Cox proportional hazards modeling was used to identify factors associated with survival. Propensity score matching was performed to address confounding variables. Survival analysis was performed using Kaplan-Meier and shared frailty models. RESULTS: Of the 4291 women analyzed, 2030 (47%) received PMRT. On MVA, PMRT (HR 0.72, p < 0.001), chemotherapy (HR 0.51, p < 0.001), and hormone therapy (HR 0.63, p < 0.001) were associated with improved overall survival (OS). After propensity score matching, a matched cohort of 2800 women was analyzed. At 5 years, OS was 83.7% and 79.8% with and without PMRT, respectively (p < 0.001). This difference in OS benefit increased with time. At 10 years, OS was 67.4% and 59.2% with and without PMRT, respectively. CONCLUSIONS: PMRT was associated with improved OS in women with pT3N0M0 breast cancer, which strongly suggests PMRT may provide a survival advantage and should be considered.

Stereotactic Body Radiotherapy for Hepatocellular Carcinoma Resulting in a Durable Relapse-Free Survival: A Case Report.

The standard of care for localized hepatocellular carcinoma (HCC) is surgical resection. For patients who decline or who are unfit for surgery, stereotactic body radiotherapy (SBRT) is emerging as a viable treatment approach. We present a case of a 77-year-old female in whom an early stage HCC was incidentally discovered. Given her religious edicts as a devout Jehovah's Witness and her subsequent desire to avoid a blood transfusion, she declined surgical resection or transplant due to the risk of hemorrhage. Ablative therapy was deemed inappropriate given the mass's size and location adjacent to the inferior vena cava and diaphragm. She was treated with definitive SBRT to a total dose of 60 Gy administered in three 20 Gy fractions every other day. She had a complete response to the treatment and remains without evidence of disease after 39 months of follow-up. Her only treatment-related side effect is a persistent CTCAE Grade 1 myositis on her back overlying the treatment area. We report this case to add to the growing body of literature suggesting SBRT as an effective and safe alternative treatment modality for HCC.