A Novel Treatment Schedule for Rapid Completion of Surgery and Radiation in Early-Stage Breast Cancer.

BACKGROUND: Data support the use of accelerated partial-breast irradiation (APBI) for early-stage breast cancer. We initiated a prospective protocol for intraoperative APBI catheter placement using a multi-lumen strut-based device. We hypothesized that with intraoperative pathology assessment of margins and sentinel nodes, all locoregional treatment (surgery and APBI) could be completed within 10 days with acceptable complication rates and cosmesis. METHODS: Eligible patients included women age 50 years or older with clinical T1 estrogen receptor positive (ER+) sentinel lymph node (SLN)-negative invasive ductal cancer or pure ductal carcinoma in situ. Patients were prospectively registered. Cosmesis was assessed using photographs graded independently by three investigators for patients with photos taken 6 months or longer after treatment. RESULTS: From October 2012 to August 2015, we enrolled 123 patients; 110 (90 %) underwent intraoperative catheter placement, whereas 13 did not due to intraoperative pathology findings. 109 APBI patients (99 %) completed their prescribed radiotherapy within 5 days, and all their locoregional therapy within 9 days, whereas one patient with a delayed positive SLN received only boost radiotherapy via catheter followed by conventional whole breast radiation. The 30-day complication rate was 6 %. In 81 patients with at least one-year followup, complications occurred in 14 (17 %) (including infection in five patients and symptomatic seroma in five patients) and correlated with device size (p = 0.05) but not with tumor size or location. The local recurrence rate was 1.8 % (two patients). Scored cosmesis was excellent or good in 88 % and fair in 12 % of patients. CONCLUSIONS: A protocol for intraoperative strut-based APBI catheter placement using careful patient selection and intraoperative pathology assessment can deliver efficient, effective treatment for early breast cancer.

Dissociable systems of working memory for rhythm and melody.

Specialized neural systems are engaged by the rhythmic and melodic components of music. Here, we used PET to measure regional cerebral blood flow (rCBF) in a working memory task for sequences of rhythms and melodies, which were presented in separate blocks. Healthy subjects, without musical training, judged whether a target rhythm or melody was identical to a series of subsequently presented rhythms or melodies. When contrasted with passive listening to rhythms, working memory for rhythm activated the cerebellar hemispheres and vermis, right anterior insular cortex, and left anterior cingulate gyrus. These areas were not activated in a contrast between passive listening to rhythms and a non-auditory control, indicating their role in the temporal processing that was specific to working memory for rhythm. The contrast between working memory for melody and passive listening to melodies activated mainly a right-hemisphere network of frontal, parietal, and temporal cortices: areas involved in pitch processing and auditory working memory. Overall, these results demonstrate that rhythm and melody have unique neural signatures not only in the early stages of auditory processing, but also at the higher cognitive level of working memory.

Delineation of Supraclavicular Target Volumes in Breast Cancer Radiation Therapy.

PURPOSE: To map the location of gross supraclavicular metastases in patients with breast cancer, in order to determine areas at highest risk of harboring subclinical disease. METHODS AND MATERIALS: Patients with axial imaging of gross supraclavicular disease were identified from an institutional breast cancer registry. Locations of the metastatic lymph nodes were transferred onto representative axial computed tomography images of the supraclavicular region and compared with the Radiation Therapy Oncology Group (RTOG) breast cancer atlas for radiation therapy planning. RESULTS: Sixty-two patients with 161 supraclavicular nodal metastases were eligible for study inclusion. At the time of diagnosis, 117 nodal metastases were present in 44 patients. Forty-four nodal metastases in 18 patients were detected at disease recurrence, 4 of whom had received prior radiation to the supraclavicular fossa. Of the 161 nodal metastases, 95 (59%) were within the RTOG consensus volume, 4 nodal metastases (2%) in 3 patients were marginally within the volume, and 62 nodal metastases (39%) in 30 patients were outside the volume. Supraclavicular disease outside the RTOG consensus volume was located in 3 regions: at the level of the cricoid and thyroid cartilage (superior to the RTOG volume), in the posterolateral supraclavicular fossa (posterolateral to the RTOG volume), and in the lateral low supraclavicular fossa (lateral to the RTOG volume). Only women with multiple supraclavicular metastases had nodal disease that extended superiorly to the level of the thyroid cartilage. CONCLUSIONS: For women with risk of harboring subclinical supraclavicular disease warranting the addition of supraclavicular radiation, coverage of the posterior triangle and the lateral low supraclavicular region should be considered. For women with known supraclavicular disease, extension of neck coverage superior to the cricoid cartilage may be warranted.

Delaying chemoradiation until after completion of adjuvant chemotherapy for pancreatic cancer may not impact local control.

BACKGROUND: Timing of administration of adjuvant chemoradiation (CRT) for pancreatic cancer has varied across studies. To date, the impact of timing of adjuvant CRT on long-term outcomes has not been evaluated. This study evaluates the effect of timing of adjuvant CRT on locoregional control (LRC) and overall survival (OS). METHODS AND MATERIALS: We performed a review of 159 patients with resected pancreatic adenocarcinoma who received adjuvant CRT between 1998 and 2010. Median dose of CRT was 50.4 Gy. The primary study variable was timing of CRT, dichotomized as immediate CRT versus delayed CRT. Consistent with Radiation Therapy Oncology Group (RTOG) 9704, immediate chemoradiation was defined as after ≤1 cycle of chemotherapy, whereas delayed CRT was defined as after >1 cycle. Cox multivariate analysis (MVA) was performed. RESULTS: Median follow-up was 55 months. Seventy-four percent of patients received immediate CRT, and 26% patients received delayed CRT. Patients treated with delayed CRT were more likely to receive adjuvant gemcitabine (100% vs 53%; P < .001). Timing of adjuvant CRT was not associated with LRC or OS on univariate or MVA. Preoperative carcinoembryonic antigen ≥1.3 ng/mL (hazard ratio, 3.18; P = .017) and positive margins (hazard ratio, 5.35; P < .001) were associated with lower rates LRC on MVA. Higher lymph node positivity ratio and not receiving adjuvant gemcitabine were independently associated with worse OS. CONCLUSIONS: Timing of adjuvant CRT for resectable pancreatic cancer may not significantly affect LRC or OS. These findings support the ongoing RTOG 0848 trial design, and provide reassurance that delaying CRT until completion of chemotherapy should not significantly impact LRC.

Impact of margin status on local recurrence after mastectomy for ductal carcinoma in situ.

PURPOSE: To examine the rate of local recurrence according to the margin status for patients with pure ductal carcinoma in situ (DCIS) treated by mastectomy. METHODS AND MATERIALS: One hundred forty-five consecutive women who underwent mastectomy with or without radiation therapy for DCIS from 1998 to 2005 were included in this retrospective analysis. Only patients with pure DCIS were eligible; patients with microinvasion were excluded. The primary endpoint was local recurrence, defined as recurrence on the chest wall; regional and distant recurrences were secondary endpoints. Outcomes were analyzed according to margin status (positive, close (≤2 mm), or negative), location of the closest margin (superficial, deep, or both), nuclear grade, necrosis, receptor status, type of mastectomy, and receipt of hormonal therapy. RESULTS: The primary cohort consisted of 142 patients who did not receive postmastectomy radiation therapy (PMRT). For those patients, the median follow-up time was 7.6 years (range, 0.6-13.0 years). Twenty-one patients (15%) had a positive margin, and 23 patients (16%) had a close (≤2 mm) margin. The deep margin was close in 14 patients and positive in 6 patients. The superficial margin was close in 13 patients and positive in 19 patients. One patient experienced an isolated invasive chest wall recurrence, and 1 patient had simultaneous chest wall, regional nodal, and distant metastases. The crude rates of chest wall recurrence were 2/142 (1.4%) for all patients, 1/21 (4.8%) for those with positive margins, 1/23 (4.3%) for those with close margins, and 0/98 for patients with negative margins. PMRT was given as part of the initial treatment to 3 patients, 1 of whom had an isolated chest wall recurrence. CONCLUSIONS: Mastectomy for pure DCIS resulted in a low rate of local or distant recurrences. Even with positive or close mastectomy margins, the rates of chest wall recurrences were so low that PMRT is likely not warranted.

Definitive high-dose photon/proton radiotherapy for unresected mobile spine and sacral chordomas.

STUDY DESIGN: A retrospective review. OBJECTIVE: The purpose of this study is to report the results of high-dose proton based definitive radiotherapy for unresected spinal chordomas. SUMMARY OF BACKGROUND DATA: Spine chordoma is treated primarily by surgical resection. However, local recurrence rate is high. Adjuvant radiotherapy improves local control. In certain locations, such as high sacrum, resection may result in significant neurological dysfunction. METHODS: We retrospectively reviewed 24 patients with newly diagnosed, previously untreated spinal chordomas (core biopsy only; no prior incision or resection) treated with high-dose definitive radiotherapy alone using protons and photons at our center from 1988 to 2009. RESULTS: Reasons for radiotherapy alone included medical inoperability (3) and concern for neurological dysfunction based on spine level (21). Median age was 69.5 years. Tumor locations included cervical (2), thoracic (1), lumbar (2), S1-S2 (17), and S3 or below (2). Median maximal tumor diameter was 6.6 cm (1.4-25.5), and median tumor volume was 198.3 cm (4.65-2061). Median total dose was 77.4 GyRBE (proton dose unit, gray relative biological effectiveness). Analysis at median follow-up of 56 months showed overall survival of 91.7% and 78.1%, chordoma specific survival of 95.7% and 81.5%, local progression free survival of 90.4% and 79.8% and metastases free survival of 86.5% and 76.3%, at 3 and 5 years respectively. Tumor volume more than 500 cm was correlated with worse overall survival. Long-term side effects included 8 sacral insufficiency fractures (none required surgical stabilization), 1 secondary malignancy, 1 foot drop, 1 erectile dysfunction, 1 perineal numbness, 2 worsening urinary/fecal incontinence, and 4 grade-2 rectal bleeding. None required new colostomy. All surviving patients remained ambulatory. CONCLUSION: These results support the use of high-dose definitive radiotherapy for patients with medically inoperable or otherwise unresected, mobile spine or sacrococcygeal chordomas.

Surgical margins and the risk of local-regional recurrence after mastectomy without radiation therapy.

PURPOSE: Although positive surgical margins are generally associated with a higher risk of local-regional recurrence (LRR) for most solid tumors, their significance after mastectomy remains unclear. We sought to clarify the influence of the mastectomy margin on the risk of LRR. METHODS AND MATERIALS: The retrospective cohort consisted of 397 women who underwent mastectomy and no radiation for newly diagnosed invasive breast cancer from 1998-2005. Time to isolated LRR and time to distant metastasis (DM) were evaluated by use of cumulative-incidence analysis and competing-risks regression analysis. DM was considered a competing event for analysis of isolated LRR. RESULTS: The median follow-up was 6.7 years (range, 0.5-12.8 years). The superficial margin was positive in 41 patients (10%) and close (≤2 mm) in 56 (14%). The deep margin was positive in 23 patients (6%) and close in 34 (9%). The 5-year LRR and DM rates for all patients were 2.4% (95% confidence interval, 0.9-4.0) and 3.5% (95% confidence interval, 1.6-5.3) respectively. Fourteen patients had an LRR. Margin status was significantly associated with time to isolated LRR (P=.04); patients with positive margins had a 5-year LRR of 6.2%, whereas patients with close margins and negative margins had 5-year LRRs of 1.5% and 1.9%, respectively. On univariate analysis, positive margins, positive nodes, lymphovascular invasion, grade 3 histology, and triple-negative subtype were associated with significantly higher rates of LRR. When these factors were included in a multivariate analysis, only positive margins and triple-negative subtype were associated with the risk of LRR. CONCLUSIONS: Patients with positive mastectomy margins had a significantly higher rate of LRR than those with a close or negative margin. However, the absolute risk of LRR in patients with a positive surgical margin in this series was low, and therefore the benefit of postmastectomy radiation in this population with otherwise favorable features is likely to be small.

Proton radiotherapy for parameningeal rhabdomyosarcoma: clinical outcomes and late effects.

PURPOSE: To report the clinical outcome and late side effect profile of proton radiotherapy in the treatment of children with parameningeal rhabdomyosarcoma (PM-RMS). METHODS AND MATERIALS: Seventeen consecutive children with PM-RMS were treated with proton radiotherapy at Massachusetts General Hospital between 1996 and 2005. We reviewed the medical records of all patients and asked referring physicians to report specific side effects of interest. RESULTS: Median patient age at diagnosis was 3.4 years (range, 0.4-17.6). Embryonal (n = 11), alveolar (n = 4), and undifferentiated (n = 2) histologies were represented. Ten patients (59%) had intracranial extension. Median prescribed dose was 50.4 cobalt gray equivalents (GyRBE) (range, 50.4-56.0 GyRBE) delivered in 1.8-2.0-GyRBE daily fractions. Median follow-up was 5.0 years for survivors. The 5-year failure-free survival estimate was 59% (95% confidence interval, 33-79%), and overall survival estimate was 64% (95% confidence interval, 37-82%). Among the 7 patients who failed, sites of first recurrence were local only (n = 2), regional only (n = 2), distant only (n = 2), and local and distant (n = 1). Late effects related to proton radiotherapy in the 10 recurrence-free patients (median follow-up, 5 years) include failure to maintain height velocity (n = 3), endocrinopathies (n = 2), mild facial hypoplasia (n = 7), failure of permanent tooth eruption (n = 3), dental caries (n = 5), and chronic nasal/sinus congestion (n = 2). CONCLUSIONS: Proton radiotherapy for patients with PM-RMS yields tumor control and survival comparable to that in historical controls with similar poor prognostic factors. Furthermore, rates of late effects from proton radiotherapy compare favorably to published reports of photon-treated cohorts.