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 \u3c1% 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 \u3c 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

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%; 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

Ultraviolet-radiation-resistant isolates revealed cellulose-degrading species of Cellulosimicrobium cellulans (UVP1) and Bacillus pumilus (UVP4)

Among extremophiles, microorganisms resistant to ultraviolet radiation (UVR) have been known to produce a variety of metabolites (i.e., extremolytes). We hypothesized that natural microbial flora on elevated land (hills) would reveal a variety of UVR-resistant extremophiles and polyextremophiles with modulated proteins and enzymes that had biotechnological implications. Microorganisms Cellulosimicrobium cellulans UVP1 and Bacillus pumilus UVP4 were isolated and identified using 16S rRNA sequencing, and showed extreme UV resistance (1.03 x 106 and 1.71 x 105 similar to J/m2, respectively) from elevated land soil samples along with unique patterns of protein expression under UVR and non-UVR. A broad range of cellulolytic activity on carboxymethyl cellulose agar plates in C. cellulans UVP1 and B. pumilus UVP4 was revealed at varying pH, temperature, and inorganic salt concentration. Further, the microbial strain B. pumilus UVP4 showed the basic characteristics of a novel group: polyextremophiles with significance in bioenergy

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

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%) ( 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

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 \u3e1 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

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

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; P5.001) and lymphovascular space invasion (hazard ratio, 1.91; 95% CI, 1.07–3.43; P5.030). Patients with a greater number of factors had worse FFDM; 5-year FFDM was 76.5% for patients with no factors (n538) versus 54.9% and 27.5% for patients with 1 (n544) and 2 factors (n526), 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