Waqar Haque

Addition of chemotherapy to definitive radiotherapy for IB1 and IIA1 cervical cancer: Analysis of the National Cancer Data Base

PURPOSEnThe standard treatment for stage IB1 and IIA1 cervical carcinoma is surgery. For non-operative cases, the National Comprehensive Cancer Network recommends definitive radiotherapy (RT) with or without chemotherapy. This study sought to determine whether the addition of chemotherapy to RT improved overall survival (OS) for patients with stage IB1 and IIA1 cervical cancer.nnnMETHODSnWe used the National Cancer Data Base to identify patients with stage IB1 or stage IIA1 cervical cancer diagnosed in 2004 to 2012 who received definitive RT with or without chemotherapy. Patient, tumor, and treatment facility characteristics were assessed. Kaplan-Meier analysis was performed to compare overall survival (OS) between groups. Cox regression analysis was performed to identify factors associated with survival. Propensity-score matching was used to compare survival outcomes while accounting for indication bias.nnnRESULTSn825 patients met the specified criteria. 275 (33.3%) of patients received treatment with RT alone, whereas 550 (66.7%) were treated with CRT. The median OS in patients treated with RT alone was 121.1months, while the median OS for patients treated with CRT was not reached (hazard ratio [HR]=0.719; 95% confidence interval [CI] 0.549-0.945). Propensity-score matched analysis confirmed that CRT was superior to RT alone (HR=0.701; 95% CI 0.509 to 0.963).nnnCONCLUSIONSnOur study suggests the addition of chemotherapy to definitive RT in patients with stage IB1 or stage IIA1 cervical cancer is associated with an improvement in OS. Prospective studies are recommended to validate these results and to further investigate the quality of life differences associated with chemotherapy use.

Radiation dose in neoadjuvant chemoradiation therapy for esophageal cancer: patterns of care and outcomes from the National Cancer Data Base

BackgroundnNeoadjuvant chemoradiotherapy (CRT) for locally advanced esophageal cancer (EC) may utilize a wide variety of RT doses, without clear consensus to date. This study evaluated national practice patterns between lower dose (LD) (40-41.4 Gy) or higher dose (HD) (50-50.4 Gy) therapy, in addition to differences in survival and postoperative events.nnnMethodsnThe National Cancer Data Base (NCDB) was queried [2004-2013] for patients with newly-diagnosed cT1a-T4aN0/N+M0 EC that received neoadjuvant CRT followed by esophagectomy. Multivariable logistic regression determined factors predictive of receiving LD RT. Kaplan-Meier analysis evaluated overall survival (OS), and Cox proportional hazards modeling determined variables associated with OS. Propensity score matching assessed groups in a balanced manner while reducing indication biases.nnnResultsnAltogether, 5,025 patients met inclusion criteria; 257 (5%) received LD RT, while 4,768 (95%) received HD RT. LD RT was more likely delivered at academic centers (P=0.038), in more recent years (2009-2013, P=0.011), and to squamous cell carcinomas (P=0.001). HD RT tended to be administered with higher T stage as well as node-positive disease (P<0.05). The median OS in the LD and HD cohorts was 39.0 vs. 35.6 months (P=0.072), and 39.0 vs. 42.7 months after propensity matching (P=0.812). Dose did not independently correlate with OS on multivariate analysis (P=0.069), but treatment at academic centers correlated with improved OS (P=0.028). There were no differences between groups in the rates of 30-day readmission (P=0.182), 30-day mortality (P=0.314), or length of postoperative hospital stay (P=0.665), but the LD group experienced lower 90-day mortality (P=0.007).nnnConclusionsnAlthough neoadjuvant LD CRT has been underutilized for EC in the United States, it is rising in more recent years. Dose did not significantly impact survival before or after propensity matching, nor did it independently predict for survival. Treatment at academic facilities independently correlated with higher survival, which has implications for patient counseling.

Management of pathologic node-positive disease following initial surgery for clinical T1-2 N0 esophageal cancer: patterns of care and outcomes from the national cancer data base

Abstract Purpose: Although clinical T1-2N0 esophageal cancer (EC) is often initially surgically resected (without neoadjuvant therapy), several studies have illustrated substantial rates of discovering pathologically node-positive disease. This study evaluated national practice patterns of adjuvant therapy for this population. Methods: The National Cancer Database (NCDB) was queried (2004–2013) for patients with cT1-2N0M0 EC that received up-front surgery (esophagectomy/local techniques) with subsequent discovery of nodal metastasis. Patients receiving any neoadjuvant therapy were excluded. Multivariable logistic regression determined factors predictive of receiving adjuvant therapy. Kaplan–Meier analysis evaluated overall survival (OS), and Cox proportional hazards modeling determined variables associated with OS. Propensity score matching assessed groups in a balanced manner while reducing indication biases. Results: Altogether, 715 patients met inclusion criteria; 114 (16%) underwent adjuvant chemotherapy, 183 (26%) chemoradiation, 16 (2%) radiotherapy alone, and 402 (56%) observation. Observation was more likely performed with advanced age (pu2009=u2009.002) and at nonacademic centers (pu2009=u2009.001). Median OS in the respective cohorts were 42.6, 35.1, 22.2, and 27.0 months. Both chemotherapy and chemoradiation were statistically similar (pu2009=u2009.462) but superior to observation (pu2009<u2009.05 for both). There was a survival benefit to any adjuvant treatment (median OS 38.5 vs. 27.0 months, pu2009<u2009.001), which persisted after propensity matching (median OS 35.1 vs. 24.3 months, pu2009<u2009.001). On multivariable analysis, any adjuvant treatment was independently associated with improved OS, along with treatment at an academic center (pu2009<u2009.05 for all). Conclusions: In the largest study to date evaluating patterns of care for pNu2009+u2009disease following resection of cT1-2N0 EC, a strikingly high proportion of patients were observed. Adjuvant treatment, ideally chemotherapy or chemoradiation, independently correlated with higher survival, and should be considered in able patients. Treatment at academic facilities also associated with higher survival, which has implications for patient counseling.

Radiation therapy utilization and outcomes for older women with breast cancer: Impact of molecular subtype and tumor grade

BACKGROUNDnRadiation therapy (RT) utilization for elderly women with respect to human epidermal growth factor receptor 2 (HER2) receptor status has not been evaluated. Our purpose was to determine differences in RT utilization and breast cancer specific survival (BCSS) for elderly breast cancer patients with distinct molecular biomarkers.nnnMETHODSnThe Surveillance, Epidemiology, and End Results database was queried for women ≥70 years of age diagnosed with T1N0M0 breast cancer between 2010 and 2013 receiving breast conservation. Chi-squared analysis was performed to determine the difference in RT utilization between groups. Multivariable logistic regression analysis was performed to determine predictors for RT use. Kaplan-Meier curves were created and the log-rank test done to compare differences in breast cancer specific survival (BCSS) between groups.nnnRESULTSnA total of 12,312 patients met the inclusion criteria. Receipt of RT for patients with distinct tumor biomarkers was as follows: 55.7% for patients with Estrogen Receptor (ER)xa0+/HER2+; 57.1% for patients with ER+/HER2-; 65.6% for patients with ER-/HER2+; and 69.2% for ER-/HER2- patients (pxa0<xa00.001). Factors associated with RT use included ER-/HER2- status, 70-74 years of age, and high grade disease, while adjuvant RT was associated with improve BCSS in ER+/HER2- and ER-/HER2- patients.nnnCONCLUSIONSnPatients 70-74 years old and those with ER-/HER2- are more likely to receive adjuvant RT. Moreover, adjuvant RT is associated with improvements in BCSS in ER+/HER2- and ER-/HER2- patients. Given possible poor compliance with hormonal therapy, the omission of RT in ERxa0+xa0patients, without consideration of HER2 status, should be undertaken with care.

The role of adjuvant chemotherapy in locally advanced bladder cancer

Abstract Purpose: The standard of care for locally advanced bladder cancer (LABC) is neoadjuvant chemotherapy followed by cystectomy. However, the role of adjuvant therapy is unclear. The purpose of this study was to evaluate the outcomes of adjuvant chemotherapy for patients with LABC following neoadjuvant chemotherapy and cystectomy, and to determine whether select patients may benefit from adjuvant chemotherapy. Methods: The National Cancer Data Base (NCDB) was queried (2004–2013) for patients with newly diagnosed pT3-4N0-3M0 bladder cancer that received neoadjuvant chemotherapy and cystectomy. Patients were divided into two groups based on the adjuvant therapy they received: chemotherapy alone or observation. Statistics included multivariable logistic regression to determine factors predictive of receiving adjuvant chemotherapy, Kaplan–Meier analysis to evaluate overall survival (OS) and Cox proportional hazards modeling to determine variables associated with OS. Results: Altogether, 2592 patients met inclusion criteria; 901 (34.8%) patients received adjuvant chemotherapy, while 1691 (65.2%) were observed. Patients treated with adjuvant chemotherapy were more likely to have positive margins were younger and more likely to receive treatment at a nonacademic facility. There was no difference in median OS between patients treated with or without adjuvant chemotherapy (22.6 vs. 21.1 months; pu2009=u2009.267). However, a longer median OS was observed with the use of adjuvant chemotherapy was observed among patients with N2–3 disease (17.5 vs. 14.4 months; pu2009=u2009.005) and positive surgical margins (16.7 vs. 12.2 months; pu2009=u2009.025). On multivariate analysis, advancing age, pT4 stage, positive N stage, positive margins and lower socioeconomic status were associated with worse OS. Conclusions: In the largest study to date evaluating efficacy of adjuvant chemotherapy, while no difference in OS was observed for adjuvant chemotherapy in all patients, a longer OS was observed among patients with N2–3 disease or with positive surgical margins. Prospective studies are recommended to further evaluate these findings.

Trends in Cardiac Mortality in Patients With Locally Advanced Non-Small Cell Lung Cancer

PURPOSEnTo use the Surveillance, Epidemiology, and End Results (SEER) database to compare cardiac-specific mortality (CSM) between left- and right-sided locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with definitive radiation therapy; and to stratify these patients over fixed time intervals to assess for differences in events by treatment era.nnnMETHODS AND MATERIALSnThe SEER database was queried for patients with stage III NSCLC who received radiation therapy to compare CSM between left- and right-sided primary cases at 5 time intervals: 1988-1992, 1993-1997, 1998-2002, 2003-2007, and 2008-2012. Cumulative incidence of CSM was compared between left- and right-sided patients using Grays test. The multivariate Fine and Gray competing risk model was used to compare CSM while accounting for other-cause mortality.nnnRESULTSnOf 884,610 lung cancer patients, 52,624 met inclusion criteria; of these, 31,549 (60%) were right-sided and 21,075 (40%) were left-sided. When evaluating CSM in each of the 5 time periods, the overall incidence of CSM decreased over time. There was a statistically significant (P<.05) difference based on laterality in all time periods except 1988-1992 (P=.14). The subdistribution hazard ratio for CSM based on disease laterality in all time periods was 1.30 (95% confidence interval 1.18-1.42) and did not discernibly differ by time interval. On multivariate analysis using the Fine and Gray competing risk model, left-sided laterality independently predicted for CSS from 1993 to 2007 (P<.05).nnnCONCLUSIONSnCardiac-specific mortality has decreased over time, and left-sided disease independently predicted for CSS during 1993-2007 but not 2008-2012. The time course of cardiac mortality seems to be early, consistent with other studies. These findings underscore the importance of minimizing cardiac irradiation during radiation treatment planning.

Concurrent Versus Sequential Chemoradiation Therapy in Completely Resected Pathologic N2 Non-Small Cell Lung Cancer: Propensity-Matched Analysis of the National Cancer Data Base

BackgroundFollowing complete resection of pN2 non-small cell lung cancer (NSCLC), national guidelines recommend either sequential (sCRT) or concurrent chemoradiotherapy (cCRT). This is the largest study to date evaluating survival between both approaches. In sCRT patients, sequencing ‘chemotherapy first’ versus ‘radiotherapy first’ was also addressed.MethodsThe National Cancer Data Base (NCDB) was queried for patients with primary NSCLC undergoing surgery (without neoadjuvant radiotherapy or chemotherapy), pN2 disease with negative surgical margins, and receiving postoperative CRT. Multivariable logistic regression ascertained factors associated with cCRT administration. Kaplan–Meier analysis evaluated overall survival (OS), and Cox proportional hazards modeling determined variables associated with OS. Propensity matching was performed to address group imbalances and indication biases.ResultsOf 1924 total patients, 1115 (58%) received sCRT and 809 (42%) underwent cCRT. Median OS in the sCRT and cCRT cohorts was 53xa0months versus 37xa0months (pxa0<xa00.001); differences persisted following propensity matching (pxa0=xa00.002). In the sCRT population, there was a trend for higher OS in the ‘chemotherapy first’ group, relative to ‘radiotherapy first’ (55 vs. 44xa0months, pxa0=xa00.079), but there were no statistically apparent differences following propensity matching (pxa0=xa00.302).ConclusionsFor completely resected pN2 NSCLC, delivering adjuvant sCRT was associated with improved survival over cCRT. Toxicity-related factors may help to explain these results but need to be better addressed in further investigations. Differential sequencing of sCRT did not appear to affect survival.

Response rates and pathologic complete response by breast cancer molecular subtype following neoadjuvant chemotherapy

PurposeThis is the largest study to date evaluating response rates and pathologic complete response (pCR) and predictors thereof, based on molecular subtype, in women with breast cancer having undergone neoadjuvant chemotherapy (NC).MethodsThe National Cancer Database was queried for women with cT1-4N1-3M0 breast cancer having received NC. Patients were divided into four subtypes: luminal A, luminal B, Her2, or triple negative (TN). Multivariable logistic regression ascertained factors associated with developing pCR. Kaplan–Meier analysis evaluated overall survival (OS) between patients by degree of response to NC when stratifying patients by subtype.ResultsOf a total of 13,939 women, 322 (2%) were luminal A, 5941 (43%) luminal B, 2274 (16%) Her2, and 5402 (39%) TN. Overall, 19% of all patients achieved pCR, the lowest in luminal A (0.3%) and the highest in Her2 (38.7%). Molecular subtype was an independent predictor of both pCR and OS in this population. Clinical downstaging was associated with improved survival, mostly in women with luminal B, Her2, and TN subtypes. Subgroup analysis of the pCR population demonstrated 5-year OS in the luminal B, Her2, and TN cohorts of 93.0, 94.2, and 90.6%, respectively (Her2 vs. TN, pu2009=u20090.016).ConclusionsAssessing nearly 14,000 women from a contemporary United States database, this is the largest known study examining the relationship between response to NC and molecular subtype. Women with luminal A disease are the least likely to undergo pCR, with the highest rates in Her2 disease. Degree of response is associated with OS, especially in luminal B, Her2, and TN patients. Despite the comparatively higher likelihood of achieving pCR in TN cases, this subgroup may still experience a survival detriment, which has implications for an ongoing national randomized trial.

Omission of chemotherapy for low-grade, luminal A N1 breast cancer: Patterns of care and clinical outcomes

PURPOSEnMultiple ongoing randomized studies are assessing the impact of omission of chemotherapy (CT) in low-risk node-positive Luminal A breast. The goal of this investigation was to evaluate trends and practice patterns of adjuvant CT use in Luminal A pT1-3N1 breast cancer, along with determining the clinical benefit from adjuvant CT in this patient population.nnnMETHODSnThe National Cancer Data Base was queried (2004-2014) for women with pT1-3N1 luminal A invasive ductal carcinoma receiving adjuvant hormonal therapy (HT). Multivariable logistic regression ascertained factors associated with adjuvant CT administration. Kaplan-Meier analysis evaluated overall survival (OS) between patients treated with CT/HT vs. HT alone, while sub-stratifying patients by age.nnnRESULTSnOf 8548 total patients, 5182 (61%) received CT/HT, while 3366 (39%) received HT alone. A steady rise in omission of adjuvant CT was observed, from 14% (2004-2005) to 41% (2012-2014). A decision not to use CT was more likely in more recent time periods, in older patients, at academic centers, following lumpectomy, and with lower T classification (pu202f<u202f0.05 for all). CT was associated with higher OS in all patients (pu202f<u202f0.001) and women ≤50 years old (pu202f=u202f0.030), but not for ages 51-60 (pu202f=u202f0.116), 61-70 (pu202f=u202f0.222), or >70 (pu202f=u202f0.239).nnnCONCLUSIONSnUsing CT for Luminal A N1 breast cancer is decreasing over time, primarily in older patients and at academic centers. Although CT is still associated with an OS advantage in all patients, subgroup analysis demonstrated no OS benefit in women >50 years of age. These results have implications on the ongoing randomized trials.

Stereotactic body radiation therapy versus conventionally fractionated radiation therapy for early stage non-small cell lung cancer

PURPOSEnTo date, no published randomized trials have shown stereotactic body radiation therapy (SBRT) to offer superior outcomes to conventionally fractionated radiation therapy (CFRT) for early-stage non-small cell lung cancer (NSCLC). The largest study to date, this investigation of a contemporary national database sought to evaluate practice patterns and survival between CFRT and SBRT.nnnMETHODSnThe National Cancer Database was queried (2004-2015) for histologically-confirmed cT1-2aN0M0 NSCLC undergoing definitive CFRT or SBRT. Multivariable logistic regression ascertained factors associated with SBRT administration. Kaplan-Meier analysis evaluated overall survival (OS) before and following propensity matching. Cox proportional hazards modeling determined variables associated with OS.nnnRESULTSnOf 23,088 patients, 2286 (10%) patients received CFRT and 20,802 (90%) SBRT. SBRT was less often delivered in African-Americans, patients with lower incomes, urban location, greater comorbidities, at non-academic centers, in larger tumors, and squamous histology (pu202f<u202f0.05 for all). Patients treated with SBRT had a higher median OS (38.8u202fmonths vs. 28.1u202fmonths, pu202f<u202f0.001). At median follow-up of 44.6u202fmonths, the median OS for the SBRT group was 38.8u202fmonths, versus 28.1u202fmonths for CFRT (pu202f<u202f0.001). These findings persisted following propensity matching. Subgroup analyses demonstrated improved OS in multiple subcohorts (T2, Charlson comorbidity score 2-3, squamous histology). SBRT was also independently associated with OS on Cox multivariate analysis (pu202f<u202f0.001).nnnCONCLUSIONSnThe largest such study to date (comprising of over 23,000 patients), this investigation demonstrates the survival benefit to ablative radiotherapy for early-stage NSCLC. Maturation of comparative prospective trials is eagerly awaited.