Prospective imaging comparison of anatomic delineation with rapid kV cone beam CT on a novel ring gantry radiotherapy device.

INTRODUCTION: A kV imager coupled to a novel, ring-gantry radiotherapy system offers improved on-board kV-cone-beam computed tomography (CBCT) acquisition time (17-40 seconds) and image quality, which may improve CT radiotherapy image-guidance and enable online adaptive radiotherapy. We evaluated whether inter-observer contour variability over various anatomic structures was non-inferior using a novel ring gantry kV-CBCT (RG-CBCT) imager as compared to diagnostic-quality simulation CT (simCT). MATERIALS/METHODS: Seven patients undergoing radiotherapy were imaged with the RG-CBCT system at breath hold (BH) and/or free breathing (FB) for various disease sites on a prospective imaging study. Anatomy was independently contoured by seven radiation oncologists on: 1. SimCT 2. Standard C-arm kV-CBCT (CA-CBCT), and 3. Novel RG-CBCT at FB and BH. Inter-observer contour variability was evaluated by computing simultaneous truth and performance level estimation (STAPLE) consensus contours, then computing average symmetric surface distance (ASSD) and Dice similarity coefficient (DSC) between individual raters and consensus contours for comparison across image types. RESULTS: Across 7 patients, 18 organs-at-risk (OARs) were evaluated on 27 image sets. Both BH and FB RG-CBCT were non-inferior to simCT for inter-observer delineation variability across all OARs and patients by ASSD analysis (p < 0.001), whereas CA-CBCT was not (p = 0.923). RG-CBCT (FB and BH) also remained non-inferior for abdomen and breast subsites compared to simCT on ASSD analysis (p < 0.025). On DSC comparison, neither RG-CBCT nor CA-CBCT were non-inferior to simCT for all sites (p > 0.025). CONCLUSIONS: Inter-observer ability to delineate OARs using novel RG-CBCT images was non-inferior to simCT by the ASSD criterion but not DSC criterion.

Oncology Trainee Perceptions of the Prior Authorization Process: A National Survey.

PURPOSE: The medical trainee perspective regarding the prior authorization process has not been previously assessed. Here we evaluate the perceptions of radiation and medical oncology trainees regarding the prior authorization process and its effect on their training and patient care. METHODS AND MATERIALS: A 12-question, nonincentivized, electronic national survey of radiation and medical oncology trainees at all Accreditation Council for Graduate Medical Education accredited oncology programs was conducted. Participation, perspectives, and experiences with the prior authorization process were assessed by Likert scale, free response, and multiple response selection. RESULTS: Between January and March of 2019, the survey was distributed to 1505 trainees at 76 institutions with responses from 174/616 radiation (28.2%) and 139/889 medical oncology trainees (15.6%). The majority (69.2%) reported participating in the prior authorization process (radiation: 78.2% vs medical: 57.6%; P < .01). Most trainees (71%) reported concern for decline in the quality of patient care due to the prior authorization process. The majority of trainees (77.1%) reported decreased enthusiasm for work and choice of profession, with a higher incidence in medical oncology trainees (83.1% vs 73.7%, P = .04). The most commonly recommended modifications by trainees included that the insurance reviewer be in the same specialty as the ordering provider (87.7%), providers be compensated for participation (82.7%), and turnaround time be more rapid (74.3%). CONCLUSIONS: These data indicate that trainees in US oncology programs are active participants in the prior authorization process and report that prior authorization approvals negatively influence their medical training and the quality of patient care. Additional efforts to revise the insurance approval process are warranted.

Radiation-Induced Brachial Plexopathy in Patients With Breast Cancer Treated With Comprehensive Adjuvant Radiation Therapy.

PURPOSE: Our purpose was to describe the risk of radiation-induced brachial plexopathy (RIBP) in patients with breast cancer who received comprehensive adjuvant radiation therapy (RT). METHODS AND MATERIALS: Records for 498 patients who received comprehensive adjuvant RT (treatment of any residual breast tissue, the underlying chest wall, and regional nodes) between 2004 and 2012 were retrospectively reviewed. All patients were treated with conventional 3 to 5 field technique (CRT) until 2008, after which intensity modulated RT (IMRT) was introduced. RIBP events were determined by reviewing follow-up documentation from oncologic care providers. Patients with RIBP were matched (1:2) with a control group of patients who received CRT and a group of patients who received IMRT. Dosimetric analyses were performed in these patients to determine whether there were differences in ipsilateral brachial plexus dose distribution between RIBP and control groups. RESULTS: Median study follow-up was 88 months for the overall cohort and 92 months for the IMRT cohort. RIBP occurred in 4 CRT patients (1.6%) and 1 IMRT patient (0.4%) (P = .20). All patients with RIBP in the CRT cohort received a posterior axillary boost. Maximum dose to the brachial plexus in RIBP, CRT control, and IMRT control patients had median values of 56.0 Gy (range, 49.7-65.1), 54.8 Gy (47.4-60.5), and 54.8 Gy (54.2-57.3), respectively. CONCLUSIONS: RIBP remains a rare complication of comprehensive adjuvant breast radiation and no clear dosimetric predictors for RIBP were identified in this study. The IMRT technique does not appear to adversely affect the development of this late toxicity.

Concurrent paclitaxel and radiation therapy for the treatment of cutaneous angiosarcoma.

INTRODUCTION: We compared clinical outcomes in patients with cutaneous angiosarcoma receiving concurrent paclitaxel-based chemoradiotherapy (CRT) vs. other modalities (Non-CRT). MATERIALS AND METHODS: Patients with non-metastatic cutaneous angiosarcoma diagnosed from 1998 to 2018 at two institutions were identified. In the CRT cohort, paclitaxel 80 mg/m2 weekly was given for up to 12 weeks and patients received radiotherapy (RT) during the final 6 weeks of chemotherapy. The RT dose was 50-50.4 Gy delivered in 1.8-2 Gy per fraction with an optional post-operative boost of 10-16 Gy. Kaplan-Meier and log-rank statistics were used to compare the outcomes between the two groups. P < 0.05 was considered statistically significant. RESULTS: Fifty-seven patients were included: 22 CRT and 35 Non-CRT. The CRT cohort had more patients > 60 years (100% vs. 60%, p < 0.001) and tumors >5 cm (68.2% vs 54.3%, p = 0.023). The median follow-up was 25.8 (1.5-155.2) months. There was no significant difference in 2-year local control (LC), distant control (DC), or progression-free survival (PFS) between the two groups. The 2-year overall survival (OS) was significantly higher for the CRT cohort (94.1% vs. 71.6%, p = 0.033). Amongst the subset of patients in the CRT cohort who received trimodality therapy, the 2-year LC, DC, PFS, and OS was 68.6%, 100%, 68.6%, and 100%, respectively. CONCLUSION: The use of concurrent paclitaxel CRT demonstrates promising outcomes. Given these results, we are currently evaluating the safety and efficacy of this regimen in prospective, phase 2 trial (NCT03921008).

Impact of invasive nodal staging on regional and distant recurrence rates after SBRT for inoperable stage I NSCLC.

PURPOSE/OBJECTIVES: Before definitive stereotactic body radiation therapy (SBRT) for presumably node-negative, early-stage NSCLC, many patients are staged with PET/CT alone. In patients undergoing PET/CT prior to SBRT, the role of invasive nodal staging (INS) with endobronchial ultrasound (EBUS) or mediastinoscopy is uncertain. We sought to characterize the impact of nodal staging modality on outcomes. MATERIALS/METHODS: Patients receiving definitive SBRT for T1-2N0 NSCLC deemed node-negative by either PET/CT plus INS (EBUS or mediastinoscopy) or PET/CT alone were identified. Patients with initially equivocal or positive nodes on PET/CT were excluded from this analysis. All patients received 3-5 fraction SBRT according to institutional guidelines. Control was assessed by at least one follow-up CT in all patients. Multivariable logistic regression (MVA) was performed to identify variables independently associated with use of INS. RESULTS: We identified 651 eligible patients at our institution from 2005-2016. INS was performed in 15.2% of patients (n = 99) with EBUS (n = 78) or mediastinoscopy (n = 21). Median follow-up was 19.4 months (0.2-135.1). Median survival was 28.5 months (0.6-140). Factors predictive of increased likelihood of INS after negative PET/CT on MVA were age (OR for decreasing age 1.033; 95% CI 1.058-1.010), Caucasian race (OR vs. non-white 1.852; 1.044-3.289), male sex (1.629; 1.031-2.575), central location (1.978; 1.218-3.211) and squamous histology (2.564; 1.243-5.287). Nodal and/or distant control at 2 years was similar between PET/CT alone (78%, 95% CI 74-82%) and INS + PET/CT (75%, 95% CI 65-85%) (p = 0.877) as well as on MVA. Overall survival did not differ based on staging modality. CONCLUSIONS: In patients with early-stage NSCLC deemed node-negative by PET/CT, addition of INS did not appreciably alter patterns of failure or survival after definitive SBRT. This study does not question the established value of INS for equivocal or suspicious nodes.

Predictors of Distant Metastases in Triple-Negative Breast Cancer Without Pathologic Complete Response After Neoadjuvant Chemotherapy.

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) predicts decreased distant metastasis. However, most patients do not experience pCR, and other risk factors for distant metastasis after NAC are poorly characterized. This study investigated factors predictive of distant metastasis in TNBC without pCR after NAC. METHODS: Women with TNBC treated with NAC, surgery, and radiation therapy in 2000 through 2013 were reviewed. Freedom from distant metastasis (FFDM) was compared between patients with and without pCR using the Kaplan-Meier method. In patients without pCR, univariate and multivariable Cox analyses were used to determine factors predictive of distant metastasis. RESULTS: We identified 153 patients with median follow-up of 4.0 years (range, 0.5-14.0 years). After NAC, 108 had residual disease (pCR, 29%). Five-year FFDM was 98% and 55% in patients with and without pCR, respectively (P<.001). Factors independently predicting FFDM in patients without pCR were pathologic nodal positivity (hazard ratio, 3.08; 95% CI, 1.54-6.14; P=.001) and lymphovascular space invasion (hazard ratio, 1.91; 95% CI, 1.07-3.43; P=.030). Patients with a greater number of factors had worse FFDM; 5-year FFDM was 76.5% for patients with no factors (n=38) versus 54.9% and 27.5% for patients with 1 (n=44) and 2 factors (n=26), respectively (P<.001). CONCLUSIONS: Lack of pCR after NAC resulted in worse overall survival and FFDM, despite trimodality therapy. In patients with residual disease after NAC, pathologic lymph node positivity and lymphovascular space invasion predicted worse FFDM.

Repeat stereotactic body radiation therapy (SBRT) for salvage of isolated local recurrence after definitive lung SBRT.

PURPOSE: Optimal management of isolated local recurrences after stereotactic body radiation therapy (SBRT) for early non-small cell lung cancer (NSCLC) is unknown and literature describing repeat SBRT for in-field recurrences after initial SBRT are sparse. We investigate the safety and efficacy of salvage SBRT for isolated local failures after initial SBRT for NSCLC. METHODS/MATERIALS: Patients receiving SBRT for isolated local recurrence after initial SBRT for early NSCLC were identified using a prospective registry. Both courses were 3-5 fractions with a biologically effective dose (BED10) of ≥100 Gy. Local failure was defined as within 1 cm of the initial planning target volume (PTV) or an overlap of the ≥25% isodose lines of the first and second treatments. Failures >1 cm beyond the PTV and without ≥25% overlap, or with additional recurrence sites were excluded. Kaplan-Meier analysis was used to estimate survival. RESULTS: A total 21 patients receiving salvage SBRT from 2008 to 2017 were identified. Median interval from initial SBRT to salvage SBRT was 23 months (7-52). Six patients (29%) had central tumors. Median follow-up time from salvage SBRT was 24 months (3-60). Median overall survival after salvage was 39 months. After reirradiation, two-year primary tumor control was 81%, regional nodal control was 89%, distant control was 75% and overall survival was 68%. Grade 2 pneumonitis occurred in 2 patients (10%) and grade 2 chest wall toxicity in 4 patients (19%). No grade 3+ toxicity was observed. CONCLUSIONS: Salvage SBRT for isolated local failures after initial SBRT appears safe, with low treatment-related toxicity and encouraging rates of tumor control.

Associations of Early Medicaid Expansion With Insurance Status and Stage at Diagnosis Among Cancer Patients Receiving Radiation Therapy.

PURPOSE: Medicaid expansion in 2014 is associated with improved insurance coverage and stage at diagnosis in cancer patients. However, little is known about the effect of early Medicaid expansions in 2010 to 2011 on outcomes in radiation therapy recipients. The objective of this study was to estimate the effect of early Medicaid expansion on insurance status and stage at diagnosis among radiation therapy recipients. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results database was queried for cases aged 18 to 64 diagnosed in 2007 to 2013 with a first primary malignancy treated with radiation therapy. Difference-in-differences analyses were used to compare changes in insurance coverage and stage at diagnosis from 2007 to 2009 and 2011 to 2013 in expansion relative to nonexpansion states. RESULTS: There was a -0.48 (95% confidence interval [CI], -0.84 to -0.13; P = .007) percentage point (PP) reduction in uninsured in expansion relative to nonexpansion states, primarily among counties with lower educational attainment (-1.73 PP; 95% CI, -2.72 to -0.75). Increases in early stage diagnoses in expansion relative to nonexpansion states were found overall and in breast (1.56 PP; 95% CI, 0.45-2.68; P = .006), colorectal (3.72 PP; 95% CI, 0.33-7.12; P = .032), and lung (1.49 PP; 95% CI, 0.25-2.72; P = .018) cancers. Decreases in late stage diagnoses were found in cervical (-5.91 PP; 95% CI, -9.58 to -2.25; P = .002), colorectal (-2.72 PP; 95% CI, -5.43 to -0.01; P = .05), and lung (-3.28 PP; 95% CI, -5.47 to -1.1; P = .003) cancers. CONCLUSIONS: For radiation therapy recipients, early Medicaid expansion was associated with decreased percent uninsured, particularly among low education counties, and earlier stage diagnoses for screenable cancers. Thus, early Medicaid expansion may improve access to care and decrease disparities for radiation therapy recipients.

Clinical outcomes and toxicity of proton beam radiation therapy for re-irradiation of locally recurrent breast cancer.

PURPOSE: Repeat radiation therapy (RT) using photons/X-rays for locally recurrent breast cancer results in increased short and long-term toxicity. Proton beam RT (PBRT) can minimize dose to surrounding organs, thereby potentially reducing toxicity. Here, we report the toxicity and clinical outcomes for women who underwent re-irradiation to the chest wall for locally recurrent breast cancer using PBRT. MATERIALS AND METHODS: This was a retrospective study analyzing 16 consecutive patients between 2013 and 2018 with locally recurrent breast cancer who underwent re-irradiation to the chest wall with PBRT. For the recurrent disease, patients underwent maximal safe resection, including salvage mastectomy, wide local excision, or biopsy only per surgeons recommendations. Systemic therapy was used per the recommendation of the medical oncologist. Patients were treated with median dose of 50.4 Cobalt Gray Equivalent (CGyE) in 28 fractions at the time of re-irradiation. Follow-up was calculated from the start of second RT course. Acute toxicities were defined as those occurring during treatment or up to 8 weeks after treatment. Late toxicities were defined as those occurring more than 8 weeks after the completion of therapy. Toxicities were based on CTCAE 4.0. RESULTS: The median age at original diagnosis and at recurrence was 49.8 years and 60.2 years, respectively. The median time between the two RT courses was 10.2 (0.7-20.2) years. The median follow-up time was 18.7 (2.5-35.2) months. No local failures were observed after re-irradiation. One patient developed distant metastasis and ultimately died. Grade 3-4 acute skin toxicity was observed in 5 (31.2%) patients. Four (25%) patients developed chest wall infections during or shortly (2 weeks) after re-irradiation. Late grade 3-4 fibrosis was observed in only 3 (18.8%) patients. Grade 5 toxicities were not observed. Hyperpigmentation was seen in 12 (75%) patients. Pneumonitis, telangiectasia, rib fracture, and lymphedema occurred in 2 (12.5%), 4 (25%), 1 (6.3%), and 1 (6.3%) patients, respectively. CONCLUSIONS: Re-irradiation with PBRT for recurrent breast cancer has acceptable toxicities. There was a high incidence of acute grade 3-4 skin toxicity and infections, which resolved, however, with skin care and antibiotics. Longer follow-up is needed to determine long-term clinical outcomes.

Single fraction high-dose-rate brachytherapy as monotherapy for low and intermediate risk prostate cancer: toxicities and early outcomes from a single institutional experience.

PURPOSE: High-dose-rate brachytherapy (HDR-BT) delivered in a single fraction as monotherapy is a potential treatment modality for low- and intermediate-risk prostate cancer (LIR-PC); however, outcome data with this technique remain limited. Here we describe our institutional HDR monotherapy experience and report the efficacy and toxicity of this treatment. MATERIAL AND METHODS: LIR-PC patients who received a definitive single fraction HDR-BT during 2013-2017 were retrospectively identified. The intended HDR monotherapy dose was 19 Gy in one fraction. Acute (< 90 days) and late (≥ 90 days) toxicity was assessed using CTCAE version 4.03. Trends in prostate-specific antigen (PSA) and American Urological Association (AUA) symptom scores after treatment were assessed using Bayesian linear mixed models. The Kaplan-Meier method was used to evaluate biochemical failure-free survival (BFFS). RESULTS: 28 patients with median follow-up of 23.6 months were identified. The median age at treatment was 65 years (48-83). The NCCN risk groups were low in 14, favorable intermediate in 10, and unfavorable intermediate in 4 patients. There were 5 (18%) and 0 (0%) acute grade 2 genitourinary (GU) and gastrointestinal (GI) toxicities, respectively, and one (4%) acute grade 3 GU toxicity. There were no late grade 3 toxicities, and 5 (18%) and 0 (0%) late grade 2 GU and GI toxicities respectively. PSA values and AUA symptom scores decreased significantly after treatment. There were 3 biochemical failures with the two- and three-year BFFS of 90.7% and 80.6%, respectively. CONCLUSIONS: Early results from a single institution suggest that single fraction HDR-BT with 19 Gy has limited toxicity, although with suboptimal biochemical control.

Predictors of Locoregional Recurrence After Failure to Achieve Pathologic Complete Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

BACKGROUND: This study evaluated factors predictive of locoregional recurrence (LRR) in women with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy who do not experience pathologic complete response (pCR). METHODS: This is a single-institution retrospective review of women with TNBC treated with neoadjuvant chemotherapy, surgery, and radiation therapy in 2000 through 2013. LRR was estimated between patients with and without pCR using the Kaplan-Meier method. Patient-, tumor-, and treatment-specific factors in patients without pCR were analyzed using the Cox proportional hazards method to evaluate factors predictive of LRR. Log-rank statistics were then used to compare LRR among these risk factors. RESULTS: A total of 153 patients with a median follow-up of 48.6 months were included. The 4-year overall survival and LRR were 70% and 15%, respectively, and the 4-year LRR in patients with pCR was 0% versus 22.0% in those without (P<.001). In patients without pCR, lymphovascular space invasion (LVSI; hazard ratio, 3.92; 95% CI, 1.64-9.38; P=.002) and extranodal extension (ENE; hazard ratio, 3.32; 95% CI, 1.35-8.15; P=.009) were significant predictors of LRR in multivariable analysis. In these patients, the 4-year LRR with LVSI was 39.8% versus 15.0% without (P<.001). Similarly, the 4-year LRR was 48.1% with ENE versus 16.1% without (P=.002). In patients without pCR, the presence of both LVSI and ENE were associated with an even further increased risk of LRR compared with patients with either LVSI or ENE alone and those with neither LVSI nor ENE in the residual tumor (P<.001). CONCLUSIONS: In patients without pCR, the presence of LVSI and ENE increases the risk of LRR in TNBC. The risk of LRR is compounded when both LVSI and ENE are present in the same patient. Future clinical trials are warranted to lower the risk of LRR in these high-risk patients.

Radiation therapy dose de-escalation compared to standard dose radiation therapy in definitive treatment of HPV-positive oropharyngeal squamous cell carcinoma.

BACKGROUND: Despite existing evidence that human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has a favorable prognosis compared to HPV-negative OPSCC, randomized studies have yet to report the effect of de-escalating radiation therapy (RT) dose for definitive treatment. The aim of this study was to assess the effectiveness of dose de-escalated RT (DDRT) vs. standard dose RT (SDRT) in patients with HPV-positive OPSCC. METHODS: This was an observational study using the National Cancer Database (Year 2010-2014) to identify patients who had HPV-positive OPSCC and were treated with definitive RT or chemo-RT. Patients undergoing surgery were excluded. Patients receiving ≥50 Gy, but <66 Gy were categorized as receiving DDRT. Patients receiving ≥66 Gy were categorized as receiving SDRT. Inverse probability of treatment weighting (IPTW) using propensity scores was used to balance the two groups. Kaplan-Meier analysis was used to estimate overall survival (OS). Subset analyses in patients receiving RT alone and concurrent chemo-RT were also performed. Multivariable Cox proportional hazards modeling was used to evaluate factors associated with OS. RESULTS: 759 patients with HPV-positive OPSCC were identified: 104 received DDRT and 655 received SDRT. The median follow-up was 30.5 (2.4-81.4) months. After IPTW-adjusted analysis, there was no difference in the 3-yr OS between the two groups (82.2% vs. 79.3%; P = 0.85). In the subset of patients receiving concurrent chemoradiotherapy, IPTW-adjusted analysis also did not show a difference in the 3-yr OS between the two groups (83.1% vs. 79.6%; P = 0.83). On multivariable analysis, DDRT was not associated with an inferior OS (HR 0.88; 95% CI, 0.53-1.47; P = 0.63). CONCLUSIONS: In this study, DDRT was not associated with an inferior OS compared to SDRT in patients with HPV-positive OPSCC. Randomized clinical trials to address DDRT in this patient population are currently ongoing.

Treatment of T3N0 non-small cell lung cancer with chest wall invasion using stereotactic body radiotherapy.

OBJECTIVES: Chest wall invasion (CWI) is observed in 5% of localized non-small cell lung cancer (NSCLC). The role of stereotactic body radiotherapy (SBRT) in these patients is unknown. We investigate the safety and efficacy of SBRT in patients with T3N0 NSCLC due to CWI. METHODS: Patients with T3N0 NSCLC due to CWI were identified using a prospective registry. CWI was defined as radiographic evidence of soft tissue invasion or bony destruction. We excluded patients with recurrent or metastatic disease. All patients were treated with definitive SBRT. Prescribed dose was 50 Gy in 5 fractions for most patients. Kaplan-Meier analysis was used to estimate survival outcomes. RESULTS: We identified 12 patients treated between 2006 and 2017. Median age was 70 (range, 58-85). Median tumor diameter was 3.0 cm (range, 0.9-7.2). Median survival was 12.0 months (range, 2.4-63). At a median follow-up of 8.9 months (range, 2.1-63), 1-year primary tumor control was 89%, involved lobar control was 89%, local-regional control was 82%, distant control was 91%, and survival was 63%. Of the 4 patients with pre-treatment chest wall pain, 3 reported improvement after SBRT. Two patients reported new grade 1-2 chest wall pain. No grade 3+ toxicity was reported, with 1 patient experiencing grade 1 skin toxicity and 3 patients experiencing grade 1-2 radiation pneumonitis. CONCLUSIONS: SBRT for CWI NSCLC is safe, with high early tumor control and low treatment-related toxicity. Most patients with pre-treatment chest wall pain experienced relief after SBRT, with no grade 3+ toxicity observed.

Clinical outcomes and patterns of care in the treatment of carcinosarcoma of the breast.

PURPOSE: Carcinosarcoma of the breast is a rare yet highly aggressive tumor accounting for <1% of all breast cancers, for which guidance on optimal management and prognosis are sparse. The purpose of this study was to investigate population-based treatment patterns and overall survival (OS) outcomes in patients with this diagnosis. MATERIALS AND METHODS: We queried the National Cancer Database for patients diagnosed with carcinosarcoma of the breast. All patients included were treated with surgery in the form of mastectomy or lumpectomy, with or without chemotherapy and/or radiation therapy. Patients with metastatic disease were excluded. Kaplan-Meier analysis was used to estimate OS. Univariate and multivariable Cox analyses were used to determine predictive factors of OS. RESULTS: A total of 329 patients from 2004 to 2012 were identified. Median age at diagnosis was 58 years (range, 24-90). Patients had T1 (21%), T2 (44%), T3 (25%), or T4 disease (10%). Most patients were node-negative at diagnosis (77%). Breast conservation surgery was utilized in 33% of patients. Chemotherapy was used in 66% of patients. Less than half (44%) of patients received radiation therapy to a median dose of 50.4 Gy (range 35-56 Gy), with a median 10 Gy boost used in 76%. With a median follow-up of 40.0 months, 3- and 5-year OS for all patients was 74% and 60%, respectively. Kaplan-Meier estimates revealed the 3-yr OS was 80% in patients receiving chemotherapy vs 59% without chemotherapy (P < 0.001). The 3-yr OS was 82% in patients receiving RT vs 66% without RT (P = 0.001). On multivariable analysis, OS was significantly influenced by Charlson-Deyo comorbidity index, insurance status, clinical T stage, surgical margin status, and treatment group, with trimodality therapy (HR: 0.45, 95% CI: 0.27-0.78; P = 0.004) and surgery plus CT (HR: 0.54, 95% CI: 0.33-0.90; P = 0.02) being associated with the greatest OS. Logistic regression revealed only younger patients were more likely to receive trimodality therapy. CONCLUSIONS: Carcinosarcoma of the breast is associated with relatively poor rates of OS. The addition of CT and RT to surgery improves OS. Trimodality therapy and surgery plus CT were associated with the greatest OS compared to surgery alone.

Treatment response as predictor for brain metastasis in triple negative breast cancer: A score-based model.

BACKGROUND: Triple negative breast cancer (TNBC) has worse prognosis than other subtypes of breast cancer, and many patients develop brain metastasis (BM). We developed a simple predictive model to stratify the risk of BM in TNBC patients receiving neo-adjuvant chemotherapy (NAC), surgery, and radiation therapy (RT). METHODS: Patients with TNBC who received NAC, surgery, and RT were included. Cox proportional hazards method was used to evaluate factors associated with BM. Significant factors predictive for BM on multivariate analysis (MVA) were used to develop a risk score. Patients were divided into three risk groups: low, intermediate, and high. A receiver operating characteristic (ROC) curve was drawn to evaluate the value of the risk group in predicting BM. This predictive model was externally validated. RESULTS: A total of 160 patients were included. The median follow-up was 47.4 months. The median age at diagnosis was 49.9 years. The 2-year freedom from BM was 90.5%. Persistent lymph node positivity, HR 8.75 (1.76-43.52, P = 0.01), and lack of downstaging, HR 3.46 (1.03-11.62, P = 0.04), were significant predictors for BM. The 2-year rate of BM was 0%, 10.7%, and 30.3% (P < 0.001) in patients belonging to low-, intermediate-, and high-risk groups, respectively. Area under the ROC curve was 0.81 (P < 0.001). This model was externally validated (C-index = 0.79). CONCLUSIONS: Lack of downstaging and persistent lymph node positivity after NAC are associated with development of BM in TNBC. This model can be used by the clinicians to stratify patients into the three risk groups to identify those at increased risk of developing BM and potentially impact surveillance strategies.

Patterns of care and survival outcomes for laryngeal small cell cancer.

BACKGROUND: To determine practice patterns and outcomes of laryngeal small cell cancer (LSCC) across the United States. METHODS: Patients with LSCC were identified in the National Cancer Database. Overall survival (OS) was compared with Kaplan-Meier analysis and Cox regression. RESULTS: From 2004 to 2014, the 5-year OS for early stage (n = 47), locally advanced stage (n = 133), and metastatic disease (n = 53) was 34%, 26%, and 9%, respectively. Chemoradiation was given in 66% of cases. Chemotherapy was less likely given in early stage disease (P = .001), and definitive radiation was less likely given in metastatic disease (P < .001). Definitive radiation improved median OS in locally advanced LSCC (20 vs. 7 months, log-rank P = .04). In multivariable modeling, radiation dose ≥40 Gy was associated with better OS (P < .001). CONCLUSION: Chemoradiation was the most common practice for treating locally advanced LSCC, and radiation dose ≥40 Gy was associated with improved OS.

Stereotactic radiosurgery and immunotherapy in melanoma brain metastases: Patterns of care and treatment outcomes.

PURPOSE: Preclinical studies have suggested that radiation therapy (RT) enhances antitumor immune response and can act synergistically when administered with immunotherapy. However, this effect in melanoma brain metastasis is not well studied. We aim to explore the clinical effect of combining RT and immunotherapy in patients with melanoma brain metastasis (MBM). MATERIALS AND METHODS: Patients with MBM between 2011 and 2013 were obtained from the National Cancer Database. Patients who did not have identifiable sites of metastasis and who did not receive RT for the treatment of their MBM were excluded. Patients were separated into cohorts that received immunotherapy versus patients who did not. Univariable and multivariable analyses were performed using Cox model to determine predictors of OS. Kaplan-Meier method was used to compare OS. Univariable and multivariable analyses using logistic regression model were used to determine the factors predictive for the use of immunotherapy. Propensity score analysis was used to account for differences in baseline patient characteristics between the RT and RT + immunotherapy groups. Significance was defined as a P value ≤ 0.05. RESULTS: A total of 1104 patients were identified: 912 received RT alone and 192 received RT plus immunotherapy. The median follow-up time was 6.4 (0.1-56.8) months. Patients with extracranial disease (OR 1.603, 95% CI 1.146-2.243, P = 0.006), and patients receiving SRS (OR 1.955, 95% CI 1.410-2.711, P < 0.001) as compared to WBRT, had a higher likelihood of being treated with immunotherapy. The utilization of immunotherapy had nearly doubled between 2011 and 2013 (12.9-22.8%). On multivariable analysis, factors associated with superior OS were younger age, lower medical comorbidities, lack of extracranial disease, and treatment with immunotherapy and SRS. The median OS was 11.1 (8.9-13.4) months in RT plus immunotherapy vs. 6.2 (5.6-6.8) months in RT alone (P < 0.001), which remained significant after propensity score matching. CONCLUSIONS: An increase in trend for the use of immunotherapy was noted, however, an overwhelming majority of the patients with this disease are still treated without immunotherapy. Addition of immunotherapy to RT is associated with improved OS in MBM. Given the selection biases that are inherent in this analysis, prospective trials investigating the combination of RT, especially SRS and immunotherapy are warranted.

Induction chemotherapy in the treatment of nasopharyngeal carcinoma: Clinical outcomes and patterns of care.

The role of induction chemotherapy in nasopharyngeal carcinoma (NPC) remains controversial. The primary aim of this study was to use the National Cancer Database to evaluate the patterns of care of induction chemotherapy in NPC and its impact on overall survival (OS). Patients with NPC from 2004 to 2014 were obtained from the NCDB. Patients were considered to have received induction chemotherapy if it was started ≥43 days before the start of RT and concurrent CRT if chemotherapy started within 21 days after the start of RT. Propensity score matching was used to control for selection bias. Cox proportional hazards model was used to determine significant predictors of OS. Logistic regression model was used to determine predictors of the use of induction chemotherapy. Significance was defined as a P value <.05. A total of 4857 patients were identified: 4041 patients (87.2%) received concurrent CRT and 816 patients (16.8%) received induction chemotherapy. The use of induction therapy remained stable between 2004 and 2014. Younger patients and those with higher T- and N-stage had a higher likelihood of being treated with induction chemotherapy. The 5-year OS in patients treated with induction chemotherapy and CRT was 66.3% vs 69.1%, respectively (P = .25). There was no difference in OS when these two groups were analyzed after propensity score matching. No differences in OS existed between these treatment groups in patients with T3-T4N1 or TanyN2-3 disease (P = .76). Propensity score matching also did not reveal any difference in OS in patients with T3-T4N1 or TanyN2-3 disease. The use of induction chemotherapy has remained stable in the last decade. In this study of patients with NPC, induction chemotherapy was not associated with improved OS compared to CRT alone.

Use of extracranial radiation therapy in metastatic melanoma patients receiving immunotherapy.

PURPOSE: Explore the patterns of use of extracranial radiation therapy (RT) in metastatic melanoma patients receiving immunotherapy, its potential association with OS, the impact of the site and timing of RT on clinical outcomes when combined with immunotherapy. MATERIALS AND METHODS: Patients with extracranial metastatic melanoma who received immunotherapy with or without extracranial RT from 2004 to 2013 were obtained from the National Cancer Database. Multivariable Cox regression analysis was used to evaluate factors associated with overall survival (OS). Subset analyses comparing outcomes in patients receiving RT to bone metastases versus soft tissue metastases were also performed. OS was compared using the Kaplan-Meier and log-rank statistics. RESULTS: A total of 1675 patients were identified: 1387 received immunotherapy alone and 288 received immunotherapy plus RT. An increase in the utilization of RT as well as SBRT was noted over time. The rate of RT use was 11.5% (0% with SBRT) in 2004 and gradually rose to 19.8% (27.0% with SBRT) in 2013 (P = 0.04). The median OS was 15.4 vs. 19.4 months in the immunotherapy plus RT and immunotherapy alone groups, respectively (P = 0.02). However, on multivariable analysis, RT was not associated with worse OS. The poor OS in the RT group was confined to the patients who received RT to bone metastases, but not in patients who received RT to soft tissue metastases. In subset analyses of patients irradiated to soft tissue, RT administered at least 30 days before immunotherapy was associated with a higher OS than RT administered within 30 days or 30 days after immunotherapy: median 26.1 months vs. 16.0 months (P = 0.009) vs. 15.4 months (P = 0.004), respectively. CONCLUSIONS: This study demonstrates that extracranial RT plays an increasing role in the management of metastatic melanoma patients in the era of immunotherapy. The site and the timing of RT may have important interaction with immunotherapy, and need to be carefully considered in future clinical trials.