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.

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.

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.

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.

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.