H. Nagar

Adjuvant Pelvic Radiation Therapy±Vaginal Brachytherapy in Patients With High-risk Stage I or Stage II Uterine Papillary Serous, Clear Cell, and High-grade Endometrioid Carcinoma.

Purpose:Radiation therapy (RT) for stages I-II uterine papillary serous carcinoma (UPSC), clear cell (CC), and high-grade endometrioid (HGE) carcinoma present a treatment challenge. Regimens include external beam radiotherapy (EBRT) with or without brachytherapy. We examine the use of these radiation modalities in these endometrial cancers (EC) with respect to cause-specific survival (CSS). Methods:The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with AJCC stages I-II UPSC, CC, or HGE cancer treated with hysterectomy and RT between 1998 and 2008. Patients who did not receive adjuvant RT or received brachytherapy alone were excluded. CSS was evaluated by the Kaplan-Meier survival analysis and the log-rank test was used to compare CSS. Multivariate analysis was performed using the Cox proportional hazards regression model. Adjusted hazard ratios (HR) were calculated for risk of EC death. Results:There were 1653 patients included in this analysis. The overall 100-month CSS for the entire cohort was 81.0%. The 100-month CSS was 85.3% for EBRT alone and 86.5% for EBRT+brachytherapy (P=0.72). Stage IC/IIA/IIB patients had a greater risk of EC death compared with stage IA/IB patients (adjusted HR=2.39; P<0.0001). Patients with UPSC and CC had a slightly higher risk of EC death compared with HGE (adjusted HR=1.01 [P=0.97] and 1.42 [P=0.02], respectively). On subset analysis, there was no difference in CSS with the addition of brachytherapy for UPSC (P=0.37), CC (P=0.27), or HGE cancer patients (P=0.42). Patients treated with brachytherapy in addition to EBRT did not demonstrate a reduced adjusted risk of EC death compared with EBRT alone (P=0.38). Conclusions:The addition of brachytherapy to adjuvant EBRT in stages I-II UPSC, CC, and HGE cancer did not demonstrate superior CSS. Thus, patients may not benefit from the addition of brachytherapy to EBRT.

The Addition Of Low Dose Total Body Irradiation To Fludarabine And Melphalan Conditioning In Haplo-Cord Transplantation For High Risk Hematological Malignancies.

Background Preliminary evidence indicates that the addition of low-dose total body irradiation (TBI) (2-4 Gy) to reduced intensity conditioning may reduce the rate of relapse in allogeneic stem cell transplants. In very high-risk patients receiving combination haploidentical single-unit cord blood transplants, we have added 4 Gy TBI to the widely used fludarabine, melphalan conditioning regimen, in hopes of reducing relapse and decreasing graft rejection. Methods We retrospectively reviewed the posttransplant outcomes of patients who underwent haplocord stem cell transplant between May 2013 and March 2015 and who received fludarabine 30 mg/m2 day (D)−7 to −3, melphalan 140 mg/m2 D−2, and 2 Gy TBI D−4 and −3. Results All 25 patients achieved primary neutrophil engraftment after a median of 12 days. The median time to platelet engraftment was 27 days. The cumulative incidence of nonrelapse mortality was 16% by D+100 and 33% by 1 year. The cumulative incidence of grade III to IV acute graft-versus-host disease was 36% by D+100. The CIR was 13% by D+100 and 29% by 1 year. The estimated 1-year overall survival and progression-free survival were 40% and 37%, respectively. In a subgroup analysis, we compared the outcome of 13 acute myeloid leukemia patients receiving this conditioning regimen with age and disease risk index–matched acute myeloid leukemia patients receiving fludarabine-melphalan without TBI. The TBI group had lower incidence of relapse at 1 year (15% vs 54%, P = 0.05). Conclusions Overall, combination fludarabine-melphalan with low-dose TBI after haplocord stem cell transplant assures good engraftment and leads to acceptable toxicity and disease control in the setting of high risk, heavily pretreated patients. These findings warrant further investigation at a larger-scale, prospective level.

Administration of concurrent vaginal brachytherapy during chemotherapy for treatment of endometrial cancer.

PURPOSE To evaluate the tolerability and toxicity of administering vaginal brachytherapy (VB) concurrently during chemotherapy compared with the sequential approach for patients with endometrial cancer. METHODS AND MATERIALS A retrospective analysis of 372 surgically staged patients with endometrial cancer American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant postoperative radiation therapy (RT) at our institution from 2001 to 2012 was conducted. All patients received VB+external beam RT (EBRT)+6 cycles of adjuvant carboplatin- and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy (range, 15-20 Gy), with 3 to 4 weekly applications, and the EBRT mean dose was 45 Gy delivered with 3-dimensional or intensity modulated RT techniques. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules. RESULTS Among patients who received RT and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%) were treated with VB during the first 3 cycles of chemotherapy, with a weekly application on nonchemotherapy days, and received the EBRT portion in a sandwiched fashion. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (P<.001; 95% confidence interval: 3.99-4.02) and sustained no difference in CTC-graded acute hematologic, GI, or GU toxicities in comparison with the patients treated with VB and chemotherapy in a sequential manner (P>.05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero. CONCLUSIONS VB during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen.

Role of Postoperative Radiotherapy in Pathologic Stage IIIA (N2) Non–Small Cell Lung Cancer in a Prospective Nationwide Oncology Outcomes Database

Introduction: The role of postoperative radiotherapy (PORT) in the treatment of pathologic stage IIIA (N2) NSCLC remains controversial. We investigated practice patterns and outcomes for these patients in a prospectively maintained nationwide oncology outcomes database. Methods: Patients with known histologic features of pathologic stage IIIA (N2) NSCLC who underwent an operation with negative margins and received adjuvant multiagent chemotherapy from 2004 to 2013 were identified from the National Cancer Data Base and stratified by the use of PORT. Multivariable logistic regression modeling was used to examine factors associated with receiving PORT, and multivariable proportional hazards regression was used to examine the association of treatment and mortality, adjusting for demographic, socioeconomic and clinicopathologic factors. Landmark analysis and covariate balancing propensity score (CBPS) weighting were also explored to account for immortal time bias and nonrandomization. Results: A total of 2691 patients were identified, with a median follow‐up of 32.32 months. In multivariable analysis, improved overall survival was associated with multiple factors, including younger age, female sex, lower Charlson‐Deyo comorbidity index, histologic type (with squamous cell being better than adenocarcinoma), smaller tumor size, lower pathologic T stage, surgical procedure (with pneumonectomy or lobectomy being better than sublobar resection), and receipt of PORT (all p < 0.05). Before landmark analysis, the hazard ratio (HR) showed an overall survival benefit for patients receiving PORT (adjusted HR = 0.83, 95% CI [confidence interval]: 0.72–0.95; p = 0.008). This benefit remained significant after CBPS weighting (HR = 0.81, 95% CI: 0.70–0.94, p = 0.005), almost significant after landmark analysis (adjusted HR = 0.84, 95% CI: 0.69–1.007, p = 0.059), and significant after landmark analysis with CBPS weighting (HR = 0.77, 95% CI: 0.63–0.94, p = 0.009). Median survival past landmark time was 27.43 months in the PORT group and 25.86 months in the non‐PORT group. Factors significantly associated with receiving PORT were facility location, facility type, Charlson‐Deyo comorbidity index, and grade (all p < 0.05). Conclusions: Improved survival is associated with receipt of PORT for patients with pathologic stage IIIA (N2) NSCLC treated with complete resection and multiagent chemotherapy.

Older Patients With Early-stage Breast Cancer: Adjuvant Radiation Therapy and Predictive Factors for Cancer-related Death

Purpose: Studies have shown that older women are undertreated for breast cancer. Few data are available on cancer-related death in elderly women aged 70 years and older with pathologic stage T1a-b N0 breast cancer and the impact of prognostic factors on cancer-related death. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried for women aged 70 years or above diagnosed with pT1a or pT1b, N0 breast cancer who underwent breast conservation surgery from 1999 to 2003. The Kaplan-Meier survival analysis was performed to evaluate breast cause-specific survival (CSS) and overall survival (OS), and the log-rank test was employed to compare CSS/OS between different groups of interest. Multivariable analysis (MVA), using Cox proportional hazards regression analysis, was performed to evaluate the independent effect of age, race, stage, grade, ER status, and radiation treatment on CSS. Adjusted hazard ratios were calculated from the MVA and reflect the increased risk of breast cancer death. Competing-risks survival regression was also performed to adjust the univariate and multivariable CSS hazard ratios for the competing event of death due to causes other than breast cancer. Results: Patients aged 85 and above had a greater risk of breast cancer death compared with patients aged 70 to 74 years (referent category) (adjusted hazard ratio [HRs]=1.98). Race had no effect on CSS. Patients with stage T1bN0 breast cancer had a greater risk of breast cancer death compared with stage T1aN0 patients (adjusted HR=1.35; P=0.09). ER negative patients had a greater risk of breast cancer death compared with ER positive patients (adjusted HR=1.59; P<0.017). Patients with higher grade tumors had a greater risk of breast cancer death compared with patients with grade 1 tumors (referent category) (adjusted HRs=1.69 and 2.96 for grade 2 and 3, respectively). Patients who underwent radiation therapy had a lower risk of breast cancer death compared with patients who did not (adjusted HR=0.55; P<0.0001). Conclusions: Older patients with higher grade, pT1b, ER-negative breast cancer had increased risk of breast cancer-related death. Adjuvant radiation therapy may provide a CSS benefit in this elderly patient population.

Disease-Free Survival According to the Use of Postmastectomy Radiation Therapy After Neoadjuvant Chemotherapy

INTRODUCTION The purpose of the study was to determine predictors of recurrence for patients treated with neoadjuvant chemotherapy (NAC) and mastectomy according to the use of postmastectomy radiation therapy (PMRT). PATIENTS AND METHODS An analysis of 161 clinically staged T1 to T3/N0 to N3 patients treated with NAC and mastectomy with and without PMRT at our institution from 2003 to 2010 was conducted. The Kaplan-Meier product limit method was used to estimate survival and time to recurrence rates and the log-rank test was used to compare groups. A Cox proportional hazard regression analysis was carried out for time to recurrence, radiation therapy, and their interaction in the model. RESULTS The median follow-up period was 48 months and 18 patients developed a recurrence. The 5-year recurrence rate and overall survival was 16.1% (95% confidence interval [CI], 9.6%-26.3%) and 93.6% (95% CI, 88.2%-97.0%), respectively. Patients who underwent PMRT had a decreased risk of recurrence compared with patients who did not (hazard ratio [HR], 0.25; 95% CI, 0.097-0.661; P < .005). The 5-year disease-free survival (DFS) rate for those who received PMRT was 91.3% (95% CI, 82.8%-95.7%) and 64.8% (95% CI, 37.8%-82.4%) for those who did not (P = .0126). Among all clinicopathologic factors examined, pathologic T stage (ypT) and pathological N stage (ypN) significantly correlated with the risk of recurrence (P < .05). Patients with any pathological nodal disease had an increased risk of recurrence compared with patients who were pathologically node-negative (HR, 7.196; 95% CI, 2.05-25.264; P < .002). CONCLUSION Patients treated with NAC and mastectomy, but without PMRT had a higher risk recurrence with increasing ypT and ypN stages. PMRT might increase DFS.

Is there a tradeoff in using modified high tangent field radiation for treating an undissected node-positive axilla?

INTRODUCTION Recent data are changing axillary management in patients with 1 to 2 positive sentinel nodes. The proposed omission of completion axillary node dissection calls into question the need for axillary nodal irradiation. This study evaluates the difference in dose to the lung and heart and risk of radiation pneumonitis (RP) for patients treated with standard tangent fields (STF) compared with modified high tangent fields (MHTF). MATERIALS AND METHODS Plans of 30 patients treated with STF were evaluated. A second plan (MHTF) was developed to include axillary levels I (Ax1) and II (Ax2). Ax1 and Ax2 volumes were contoured based on the RTOG (Radiation Therapy Oncology Group) Atlas guidelines. Dose-volume histograms of the 2 plans were used to compare doses received by Ax1, Ax2, lung, and heart volumes. The risk of RP was calculated using normal tissue complication probability (NTCP) modeling. RESULTS The D95 (dose to 95% of volume) received by Ax1 and Ax2 volumes increased from 16.38 Gy and 5.71 Gy for STF to 49.38 Gy and 48.08 Gy for MHTF, respectively. Mean lung dose increased from 5.40 Gy for STF to 9.47 Gy for MHTF. Mean ipsilateral lung V5, V10, and V20 values increased from 19%, 14%, and 10%, respectively, for STF, to 32%, 24%, and 18%, respectively, for MHTF. Mean heart dose increased from 1.98 Gy for STF to 3.93 Gy for MHTF. Mean heart V25 and V30 values increased from 2% and 1%, respectively, for STF, to 4% and 3%, respectively, for MHTF. NTCP for RP increased from near 0% for STF to 1% for MHTF. CONCLUSION Modified high tangent fields are necessary for definitive coverage of Ax1 and Ax2. This technique increases mean ipsilateral lung and heart doses as well as the V5, V10, and V20 of ipsilateral lung and the V25 and V30 of the heart. Risk of RP remains low by use of MHTF.

Omission of Adjuvant Radiotherapy in the Elderly Breast Cancer Patient: Missed Opportunity?

Purpose We used the National Cancer Data Base to analyze practice patterns of adjuvant breast radiotherapy (RT) in elderly patients to see if a difference in overall survival (OS) could be detected. Additionally, we investigated factors that affected OS in these patients. Patients and Methods Women aged ≥ 65 years with hormone receptor–positive and human epidermal growth factor receptor 2 (HER2)‐negative pathologic T1‐T2N0M0 invasive breast cancer measuring up to 3 cm who were treated with breast conservation and adjuvant endocrine therapy without adjuvant chemotherapy were identified and stratified by use of adjuvant RT. Multivariable Cox proportional hazards modeling was used to examine the association of treatment and mortality adjusting for demographic, socioeconomic, and clinicopathologic factors. Kaplan‐Meier analysis was used to estimate overall 5‐year survival in patients who did or did not receive adjuvant RT, and to compare those groups. Results A total of 61,395 patients with a median follow‐up of 48.7 months (range, 0‐107 months) were identified. On Cox regression analysis, improved OS was associated with treatment at an academic facility, younger age, higher income level, lower Charlson‐Deyo comorbidity index, and receipt of adjuvant RT (all P < .05). The overall 5‐year survival rate was 93.0% (95% confidence interval 92.7‐93.3) in the adjuvant RT group and 83.6% (95% confidence interval 82.5‐84.7) in the nonadjuvant RT group (P < .0001). Conclusion Improved survival is associated with the receipt of adjuvant RT for older women with early‐stage hormone receptor–positive HER2‐negative breast cancer who received adjuvant endocrine therapy. However, there are many limitations inherent to a retrospective database study such as ours, so the findings should be taken with caution. Micro‐Abstract We used the National Cancer Data Base to extract data from over 60,000 patients treated with or without adjuvant radiotherapy (RT) after breast‐conserving surgery. Our exploratory analysis revealed a 5‐year overall survival rate of 93.0% in the adjuvant RT group and 83.6% in the nonadjuvant RT group.

Practice patterns and outcomes for patients with node-negative hormone receptor-positive breast cancer and intermediate 21-gene Recurrence Scores

BackgroundThe recommendation for chemotherapy in early-stage breast cancer patients has been refined by the 21-gene Recurrence Score. However, uncertainty remains whether patients in the Intermediate Risk category benefit from chemotherapy.MethodsWe analyzed female patients from the National Cancer Database from 2006 to 2012 who had pT1c-T2N0M0 breast cancer, were ER/PR-positive and HER2-negative, received endocrine therapy, and had a 21-gene Recurrence Score from 11 to 25. We performed univariate and multivariate logistic regression analyses to see what impacted chemotherapy receipt. We compared overall survival using Kaplan–Meier curves and the log-rank test. A multivariable Cox proportional hazards regression model was used to assess what variables impacted overall survival.ResultsOf 21,991 patients who met all inclusion and exclusion criteria, 4646 (21.1%) received chemotherapy and 17,345 (78.9%) did not. Chemotherapy was more often received by patients who were younger (adjusted odds ratios (aORs) compared to age < 40 years, 0.48 for 40s, 0.34 for 50s, 0.20 for 60s, 0.10 for 70s, and 0.07 for 80+), had private insurance vs Medicare (aOR = 1.37), were from metro vs urban counties (aOR = 1.15), and were treated in community cancer centers vs academic programs (aOR = 1.26), and those with tumors of higher grade (grade 2 vs 1, aOR = 1.72; grade 3 vs 1, aOR = 3.76), higher tumor stage (pT2 vs pT1c, aOR = 1.62), or presence of lymphovascular invasion (LVI) (aOR = 1.41). At a median follow-up of 46.4 months, there was no significant difference in overall survival between patients who received chemotherapy vs those who did not (5-year estimated overall survival, 97.4% vs 97.8%, p = 0.89). On multivariable analysis, worse overall survival was associated with Black race, treatment at a community program, Medicaid, high-grade tumors, pT2 vs pT1c, higher Charlson–Deyo score, and no radiotherapy. Utilization trends showed that chemotherapy receipt in these patients has been decreasing from 25.8% in 2010 to 18.4% in 2013 (p < 0.001).ConclusionsIn these patients where the benefit of chemotherapy remains uncertain, current practices see chemotherapy more likely to be used in patients with younger age, higher pathologic T stage, higher grade tumors, and LVI. No apparent difference was seen in overall survival between those who received chemotherapy and those who did not.

The State of Surgical Axillary Management and Adjuvant Radiotherapy for Early-stage Invasive Breast Cancer in the Modern Era

&NA; Sentinel lymph node biopsy has been shown in the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial to be sufficient for women with early‐stage breast cancer and 1 to 2 positive sentinel lymph nodes; however, many patients received non‐specified radiotherapy. Practice patterns since the publication of this study were analyzed using a large nationwide database showing a decrease in completion axillary lymph node dissection and marked variability in radiotherapy field design. Background: For clinical T1‐2N0 breast cancer, sentinel lymph node biopsy (SLNB) has been shown in American College of Surgeons Oncology Group (ACOSOG) Z0011 to be sufficient for women with 1 to 2 positive sentinel lymph nodes with no added benefit for completion axillary lymph node dissection (ALND). Z0011 specified whole breast radiotherapy (RT) using standard tangential fields; however, later analysis showed variation in field design. We assessed nationwide practice patterns and examined factors associated with patients undergoing completion ALND and subsequent radiation field design. Patients and Methods: Women with clinical T1‐2N0 breast cancer who underwent breast‐conserving surgery, axillary staging, and whole breast RT in 2012 to 2013 were identified in the National Cancer Database. Multivariable logistic regression modeling was used to examine axillary management and RT, adjusting for demographic and clinicopathologic factors. Results: Among 83,555 patients meeting criteria, 9.3% underwent upfront ALND, 75.8% underwent SLNB only, and 14.9% underwent SLNB with completion ALND. From 2012 to 2013, upfront SLNB increased from 90.1% to 91.4% (odds ratio, 1.14; P < .001). Among 9474 patients that underwent SLNB with 1 to 2 positive sentinel nodes, 31.2% received completion ALND. Among patients with 1 to 2 positive sentinel nodes, SLNB increased from 65.8% to 72.1% from 2012 to 2013 (P < .001). For patients with 1 to 2 positive lymph nodes that underwent SLNB only, 63.4% underwent breast RT, whereas 36.6% received breast and nodal RT. Conclusions: Nationwide practice patterns of axillary management vary. Despite an increasing rate of SLNB, many patients still receive upfront and completion ALND. Furthermore, there is significant variation in RT field design, and modern treatment guidelines are warranted for this patient population.