Comparative Evaluation of Proton Therapy and Volumetric Modulated Arc Therapy for Brachial Plexus Sparing in the Comprehensive Reirradiation of High-Risk Recurrent Breast Cancer.

Purpose: Recurrent or new primary breast cancer requiring comprehensive regional nodal irradiation after prior radiation therapy (RT) to the supraclavicular area and upper axilla is challenging due to cumulative brachial plexus (BP) dose tolerance. We assessed BP dose sparing achieved with pencil beam scanning proton therapy (PBS-PT) and photon volumetric modulated arc therapy (VMAT). Methods and Materials: In an institutional review board-approved planning study, all patients with ipsilateral recurrent breast cancer treated with PBS-PT re-RT (PBT1) with at least partial BP overlap from prior photon RT were identified. Comparative VMAT plans (XRT1) using matched BP dose constraints were developed. A second pair of proton (PBT2) and VMAT (XRT2) plans using standardized target volumes were created, applying uniform prescription dose of 50.4 per 1.8 Gy and a maximum BP constraint <25 Gy. Incidence of brachial plexopathy was also assessed. Results: Ten consecutive patients were identified. Median time between RT courses was 48 months (15-276). Median first, second, and cumulative RT doses were 50.4 Gy (range, 42.6-60.0), 50.4 Gy relative biologic effectiveness (RBE) (45.0-64.4), and 102.4 Gy (RBE) (95.0-120.0), respectively. Median follow-up was 15 months (5-33) and 18 months for living patients (11-33) Mean BP max was 37.5 Gy (RBE) for PBT1 and 36.9 Gy for XRT1. Target volume coverage of V85% (volume receiving 85% of prescription dose), V90%, and V95% were numerically lower for XRT1 versus PBT1. Similarly, axilla I-III and supraclavicular area coverage were significantly higher for PBT2 than XRT2 at dose levels of V55%, V65%, V75%, V85%, and V95%. Only axilla I V55% did not reach significance (P = .06) favoring PBS-PT. Two patients with high cumulative BPmax (95.2 Gy [RBE], 101.6 Gy [RBE]) developed brachial plexopathy symptoms with ulnar nerve distribution neuropathy without pain or weakness (1 of 2 had symptom resolution after 6 months without intervention). Conclusions: PBS-PT improved BP sparing and target volume coverage versus VMAT. For patients requiring comprehensive re-RT for high-risk, nonmetastatic breast cancer recurrence with BP overlap and reasonable expectation for prolonged life expectancy, PBT may be the preferred treatment modality.

Prognostic implications of HER2NEU-low in metastatic breast cancer.

INTRODUCTION: We explored characteristics and clinical outcomes of HER2-negative and HER2-low metastatic breast cancers using real-world data. METHODS: We queried the National Cancer Database to identify MBC patients that were HER2-low or HER2-negative per immunohistochemical staining. A binomial regression analysis identified demographic and clinical correlates of each subtype. A Cox multivariable regression analysis (MVA) and propensity-match analysis were performed to identify correlates of survival. RESULTS: Excluding missing data, 24,636 MBC patients diagnosed between 2008 and 2015 were identified; 27.9% were HER2-negative and 72.1% were HER2-low. There were no relevant demographic differences between the groups. HER2-low tumors were half as likely to have concomitant hormone receptor-positive status (p < 0.01). The 3-year survival rate among hormone receptor-negative patients was 33.8% for HER2-low and 32.2% for HER2-negative (p < 0.05), and 60.9% and 55.6% in HER2-low and HER2-negative cases among hormone receptor-positive patients (p < 0.05), respectively. HER2-low cases were associated with better survival on MVA (HR =0.95, 95% CI 0.91-0.99) and remained superior with propensity-matching (HR = 0.92, 95% CI 0.89-0.96). In a subset analysis isolated to hormone receptor-positive cases, HER2-low remained correlated with improved survival (HR = 0.93, 95% CI 0.89-0.98) with propensity-matched MVA. Correlates of worse survival include older age as a continuous variable (HR = 1.02, 95% CI 1.02-1.02) and Black race (HR = 1.26, 95% CI 1.20-1.32) [all p < 0.01]. CONCLUSIONS: In the largest such analysis performed to date, our study demonstrates a small but statistically significant association with improved survival for HER2-low tumors compared to HER2-negative tumors in MBC.

Proton pencil beam scanning craniospinal irradiation (CSI) with a single posterior brain beam: Dosimetry and efficiency.

This study explores the feasibility and potential dosimetric and time efficiency benefit of proton Pencil Beam Scanning (PBS) craniospinal irradiation with a single posterior-anterior (SPA) brain field. The SPA approach was compared to our current clinical protocol using Bilateral Posterior Oblique brain fields (BPO). Ten consecutive patients were simulated in the head-first supine position on a long BOS frame and scanned using 3 mm CT slice thickness. A customized thermoplastic mask immobilized the patient's head, neck, and shoulders. A vac-lock was used to secure the legs. PBS proton plans were robustly optimized with 3mm setup errors and 3.5% range uncertainties in the Eclipse V15.6 treatment planning system (n = 12 scenarios). In order to achieve a smooth gradient dose match at the junction area, at least 5 cm overlap region was maintained between the segments and 5 mm uncertainty along the cranial-cauda direction was applied to each segment independently as additional robust optimization scenarios. The brain doses were planned by SPA or BPO fields. All spine segments were planned with a single PA field. Dosimetric differences between the BPO and SPA approaches were compared, and the treatment efficiency was analyzed according to timestamps of beam delivery. Results: The maximum brain dose increases to 111.1 ± 2.1% for SPA vs. 109.0 ± 1.7% for BPO (p < 0.01). The dose homogeneity index (D5/D95) in brain CTV was comparable between techniques (1.037 ± 0.010 for SPA and 1.033 ± 0.008 for BPO). Lens received lower maximum doses by 2.88 ± 1.58 Gy (RBE) (left) and 2.23 ± 1.37 Gy (RBE) (right) in the SPA plans (p < 0.01). No significant cochlea dose change was observed. SPA reduced the treatment time by more than 4 minutes on average and ranged from 2 to 10 minutes, depending on the beam waiting and allocation time. SPA is dosimetrically comparable to BPO, with reduced lens doses at the cost of slightly higher dose inhomogeneity and hot spots. Implementation of SPA is feasible and can help to improve the treatment efficiency of PBS CSI treatment.

Case Report: Bilateral targeted intraoperative radiotherapy: a safe and effective alternative for synchronous bilateral breast cancer.

Background: The incidence of bilateral breast cancer (BBC) ranges from 1.4% to 11.8%. BBC irradiation is a challenge in current clinical practice due to the large target volume that must be irradiated while minimizing the dose to critical organs. Supine or prone breast techniques can be used, with the latter providing better organ sparing; both, however, result in lengthy treatment times. The use of Intra-operative radiotherapy (IORT) in breast cancer patients who choose breast conservation has been highlighted in previous studies, but there is a scarcity of literature analyzing the utility and applicability of IORT in BBC. This case series aims to highlight the applicability of administering bilateral IORT in patients with BBC. Case reports: Five patients with bilateral early-stage breast cancer (or DCIS) were treated with breast-conserving surgery followed by bilateral IORT. Of the 10 breast cancers, 8 were diagnosed as either DCIS or IDC, while the other 2 were diagnosed as invasive lobular carcinoma and invasive carcinoma, respectively. During surgery, all patients received bilateral IORT. Furthermore, 1 patient received external beam radiation therapy after her final pathology revealed grade 3 DCIS. The IORT procedure was well tolerated by all five patients, and all patients received aromatase inhibitors as adjuvant therapy. Additionally, none of these patients showed evidence of disease after a 36-month median follow-up. Conclusion: Our findings demonstrate the successful use of IORT for BCS in patients with BBC. Furthermore, none of the patients in our study experienced any complications, suggesting the feasibility of the use of IORT in BBC. Considering the benefits of improved patient compliance and a reduced number of multiple visits, IORT may serve as an excellent patient-centered alternative for BBC. Future studies are recommended to reinforce the applicability of IORT in patients with BBC.

Effect of treatment interruptions on overall survival in patients with triple-negative breast cancer.

INTRODUCTION: Currently, there are no data regarding the impact of treatment interruptions during radiotherapy for breast cancer. In this study, we examine the correlation between treatment interruptions during radiotherapy and outcomes in triple-negative breast cancer patients. METHODS: A total of 35 845 patients with triple-negative breast cancer treated between 2010 and 2014 were identified and analyzed from the National Cancer Database. The number of interrupted radiotherapy treatment days was calculated as the difference between the total elapsed days from the start to end of radiation treatment (both initial treatment and boost treatment, when boost was administered) and the total number of expected treatment days, defined as the number of expected treatment days with an addition of 2 weekend days for every multiple of 5 treatment days. Binomial multivariate regression analysis was used to detect correlates of treatment interruptions, and propensity-score matched multivariable Cox proportional hazard models were used to evaluate the association between treatment interruption and overall survival (OS). RESULTS: When modeled as a continuous variable, longer treatment duration was associated with poorer OS (hazard ratio [HR] = 1.023, 95% confidence interval [CI] = 1.015 to 1.031). In reference to 0-1 days of interruption, patients with 2-5 interrupted days (HR = 1.069, 95% CI = 1.002 to 1.140 interrupted days), 6-10 interrupted days (HR = 1.239, 95% CI = 1.140 to 1.348 interrupted days), and 11-15 interrupted days (HR = 1.265, 95% CI = 1.126 to 1.431 interrupted days) experienced increasing likelihood of mortality. CONCLUSION: In the first study of its kind, we report a correlation between treatment interruptions during adjuvant radiotherapy in triple-negative breast cancer and OS.

Experience with intraoperative radiation therapy in an urban cancer center.

BACKGROUND/OBJECTIVE: Intra-operative radiation therapy (IORT) is a newer partial breast irradiation technique that has been well studied in 2 large randomized trials, the TARGIT-A and ELIOT trials. We initiated our IORT program in 2018 in the context of a registry trial, and aim to report our early results thus far. METHODS: We instituted an IORT practice using Intrabeam® low energy 50kVp x-rays for selected breast cancer cases in 2018. Patients were enrolled on our institutional registry protocol which allowed for IORT in ER + patients with grade 1-2 DCIS ≤ 2.5 cm or invasive disease ≤ 3.5 cm in patients of at least 45 years of age. RESULTS: Between January 2018 and December 2021, 181 patients with clinical stage 0-IIA ER + breast cancer were evaluated. One hundred sixty-seven patients ultimately received IORT to 172 sites. The majority of patients received IORT at the time of initial diagnosis and surgery (160/167; 95.8%). Re-excision post IORT occurred in 16/167 patients (9.6%) due to positive margins. Adjuvant RT to the whole breast +/- LN was ultimately given to 23/167 (13.8%) patients mainly due to positive sentinel LN found on final pathology (12/23; 52%); other reasons were close margins for DCIS (3/23; 13%), tumor size (3/23; 4.3%), and multifactorial (5/23; 17.4%). Five patients (3%) had post-operative complications of wound dehiscence. There were 3 local recurrences (1.6%) at a median follow-up of 27.9 months (range: 0.7- 54.8 months). CONCLUSIONS: IORT has been proven to be a safe and patient-centered form of local adjuvant RT for our population, in whom compliance with a longer course of external beam radiation can be an issue. Long term efficacy remains to be evaluated through continued follow up. In the era of COVID-19 and beyond, IORT has been an increasingly attractive option, as it greatly minimizes toxicities and patient visits to the clinic. TRIAL REGISTRATION: All patients were prospectively enrolled on an institutional review board-approved registry trial (IRB number: 2018-9409).

Predictors of Financial Toxicity in Patients Receiving Concurrent Radiation Therapy and Chemotherapy.

Purpose: Financial toxicity (FT) is a significant concern for patients with cancer. We reviewed prospectively collected data to explore associations with FT among patients undergoing concurrent, definitive chemoradiation therapy (CRT) within a diverse, urban, academic radiation oncology department. Methods and Materials: Patients received CRT in 1 of 3 prospective trials. FT was evaluated before CRT (baseline) and then weekly using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Core-30 questionnaire. Patients were classified as experiencing FT if they answered ≥2 on a Likert scale question (1-4 points) asking if they experienced FT. Rate of change of FT was calculated using linear regression; worsening FT was defined as increase ≥1 point per month. χ2, t tests, and logistic regression were used to assess predictors of FT. Results: Among 233 patients, patients attended an average of 9 outpatient and 4 radiology appointments over the 47 days between diagnosis and starting CRT. At baseline, 52% of patients reported experiencing FT. Advanced T stage (odds ratio, 2.47; P = .002) was associated with baseline FT in multivariate analysis. The mean rate of FT change was 0.23 Likert scale points per month. In total, 26% of patients demonstrated worsening FT during CRT. FT at baseline was not associated with worsening FT (P = .98). Hospitalization during treatment was associated with worsening FT (odds ratio, 2.30; P = .019) in multivariate analysis. Conclusions: Most patients reported FT before CRT. These results suggest that FT should be assessed (and, potentially, addressed) before starting definitive treatment because it develops early in a patient's cancer journey. Reducing hospitalizations may mitigate worsening FT. Further research is warranted to design interventions to reduce FT and avoid hospitalizations.

Case Report: Can Targeted Intraoperative Radiotherapy in Patients With Breast Cancer and Pacemakers be the New Standard of Care?

Background: Partial breast irradiation with Intra-operative radiotherapy (IORT) has become a popular management option as opposed to whole breast radiation using external beam radiotherapy for breast cancer patients. While previous studies have highlighted the use of IORT in breast cancer patients, there is a scarcity of literature on the use of IORT in those who also have ipsilateral pacemakers. Thus, the aim of our case report is to highlight the applicability of IORT in breast cancer patients who also have a pacemaker. Case Reports: Two female patients with an implanted dual-chamber pacemaker presented with a diagnosis of left-sided invasive ductal carcinoma on mammogram. Mammography of the left breast revealed a 10 mm and 7 mm spiculated mass, respectively, further confirmed with an ultrasound-guided core biopsy that was conclusive of clinical Stage I T1 N0 grade 2, ER +, PR + Her2 - invasive ductal carcinoma. They met our eligibility criteria for IORT, which is being performed as a registry trial. These patients underwent a wide excision lumpectomy along with IORT. Conclusion: Our findings underscore the successful use of targeted IORT for breast-conserving surgery in a patient with invasive ductal carcinoma and pacemaker, hence eliminating the necessity for relocating pacemaker surgeries in these patients. Furthermore, no device failure or malfunction for the pacemaker was recorded before, during, or after the surgery, demonstrating the safety of using IORT in patients with preinstalled pacemaker despite a lack of evidence on safe radiation dosage or manufacturer guidelines. Nonetheless, the effects of IORT on pacemaker < 10 cm were not studied in our patients and further clinical studies are recommended to reinforce the applicability and safe distance of IORT in breast cancer patients with pacemaker.

Successful Total Knee Arthroplasty in a Patient With Contralateral Ankylosis Due to Severe Heterotopic Ossification.

A 63-year-old woman with ankylosis of the left knee due to severe heterotopic ossification (HO) following total knee arthroplasty (TKA) underwent right TKA with preoperative radiation and postoperative chemical prophylaxis for HO. At the one-year follow-up, the patient had no evidence of HO in the right knee. To our knowledge, there are no reports of successful arthroplasty in patients with a history of ankylosis due to severe HO. We present the first case of successful TKA in a patient with ankylosis of the contralateral knee. TKA can be safely performed in patients at high risk for developing ankylosis.

Phantosmia Among Pediatric, Adolescent, and Young Adult Patients Receiving Proton Beam Therapy.

Purpose: Phantosmia, an underreported toxicity of brain radiation therapy (RT), is defined as an olfactory disorder resulting in a malodorous phantom smell. This study aimed to characterize the incidence of phantosmia in patients treated with intensity modulated proton therapy (IMPT). Methods and Materials: In this institutional review board-approved retrospective study, the electronic medical record of a pencil beam scanning-only proton center was queried for patients ≤39 years of age who received IMPT for primary intracranial, metastatic intracranial, skull base, nasopharyngeal or sinonasal neoplasms between August 2019 and December 2020. Patient, clinical, and phantosmia-related characteristics were collected. The olfactory region was defined to include the olfactory bulb and tract. Phantosmia severity was graded by intervention use (mild, no intervention; moderate, supportive treatment; severe, RT discontinuation). Results: Ninety-nine patients met the inclusion criteria. Twelve patients (12.1%) reported phantosmia. Patients described perceiving a "chlorine," "broccoli," "stale water," "metallic," or "noxious" smell. Of the patients who reported phantosmia, median age was 17 (12-33) years, 66.7% were male, and 91.7% had intracranial tumors. None of the patients had prior RT. Chemoradiotherapy treatment did not correlate with phantosmia development (odds ratio, 1.09; 95% confidence interval, 0.32-3.70; P = .90). Ten patients experienced accompanying toxicities, including taste changes (n = 3), vision disturbances (n = 5), and nausea/emesis (n = 7). Phantosmia was mild (n = 7) or moderate (n = 5). All patients completed their RT course. Sixty-seven percent received craniospinal irradiation (CSI) while 33% received focal brain RT, with the olfactory region receiving doses as low as 0.5 Gy. Notably, 8 of 27 patients who received CSI (30%) reported phantosmia (odds ratio, 7.66; 95% confidence interval, 2.07-28.34; P = .002). Conclusions: In the first-ever study examining radiation-induced phantosmia among children and young adults treated with IMPT, all affected patients received irradiation dose to the olfactory region. Physician awareness of phantosmia, especially in the context of CSI, may improve the patient experience and treatment compliance. A prospective study is needed to elucidate frequency, severity, and phantosmia mechanism.

Percutaneous Screw Stabilization of Non-Periacetabular Pelvic Lesions Caused by Metastatic Cancer and Multiple Myeloma.

BACKGROUND: The pelvis is one of the most common locations for metastatic bone disease. While many of the publications that describe surgical treatments focus on periacetabular lesions (Enneking zone II), there is a lack of investigation into lesions in the non-periacetabular areas (zones I, III, and IV). We recently described a minimally invasive percutaneous screw application for metastatic zone-II lesions with excellent results. In the present study, we aimed to extend this approach to the other pelvic areas. METHODS: Twenty-two consecutive patients with painful non-periacetabular pelvic metastatic cancer were included based on retrospective chart review. There were 16 women and 6 men with an average age of 60 years (range, 36 to 81 years). The most common primary cancers were multiple myeloma (7 cases) and breast (5 cases). The most common locations were the sacrum and the ilium. A pathologic fracture was identified in 15 patients. Most of the lesions were treated with multiple large-diameter screws, except for the isolated zone-III lesions. All of the procedures were completed in a standard operating room without the need for special instruments. Radiation therapy was given to 19 patients; the average dose was 15 Gy. The studied outcomes were pain and functionality as assessed by a visual analog scale (VAS) score and the Eastern Cooperative Oncology Group score (ECOG), respectively. RESULTS: There were no surgical complications and no need for blood transfusion. The average follow-up time was 7 months (range, 0.3 to 34.0 months). Two patients died within 4 weeks of surgery due to COVID-19 infection. There was significant improvement in the postoperative VAS pain score (p < 0.0001) and the ECOG score (p < 0.05) when compared with the preoperative scores. There was no implant failure or revision surgery. Local bone-healing was observed in 12 of 14 patients (86%) who survived for >3 months after surgery. CONCLUSIONS: Percutaneous screw application is safe and effective in the treatment of metastatic non-periacetabular pelvic lesions. Given the simplicity of the technique and the instrumentation and the tolerance for concomitant treatments, this approach is worthy of broader consideration. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Breast cancer survivorship care during the COVID-19 pandemic within an urban New York Hospital System.

PURPOSE: To examine clinicodemographic determinants associated with breast cancer survivorship follow-up during COVID-19. METHODS: We performed a retrospective, population-based cohort study including early stage (Stage I-II) breast cancer patients who underwent resection between 2006 and 2018 in a New York City hospital system. The primary outcome was oncologic follow-up prior to and during the COVID-19 pandemic. Secondary analyses compared differences in follow-up by COVID-19 case rates stratified by ZIP code. RESULTS: A total of 2942 patients with early-stage breast cancer were available for analysis. 1588 (54%) of patients had attended follow-up in the year prior to the COVID-19 period but failed to continue to follow-up during the pandemic, either in-person or via telemedicine. 1242 (42%) patients attended a follow-up appointment during the COVID-19 pandemic. Compared with patients who did not present for follow-up during COVID-19, patients who continued their oncologic follow-up during the pandemic were younger (p = 0.049) more likely to have received adjuvant radiation therapy (p = 0.025), and have lower household income (p = 0.031) on multivariate modeling. When patients who live in Bronx, New York, were stratified by ZIP code, there was a modest negative association (r = -0.56) between COVID-19 cases and proportion of patients who continued to follow-up during the COVID-19 period. CONCLUSION: We observed a dramatic disruption in routine breast cancer follow-up during the COVID-19 pandemic. Providers and health systems should emphasize reintegrating patients who missed appointments during COVID-19 back into regular surveillance programs to avoid significant morbidity and mortality from missed breast cancer recurrences.

The effect of low-dose radiation spillage during stereotactic radiosurgery for brain metastases on the development of de novo metastases.

PURPOSE/OBJECTIVES: Stereotactic radiosurgery (SRS) for metastatic disease to the brain is associated with higher in-brain failures compared to whole brain radiation therapy (WBRT). Here we investigated the relationship between low-dose fall off during SRS and location of new brain lesions. MATERIALS AND METHODS: One hundred sixty-seven patients treated with single fraction or fractionated SRS for intact or resected brain metastases at our institution from January 2016 to June 2018 were reviewed. Patients with imaging findings of new brain metastases after the initial SRS were included. Patients with WBRT before SRS were excluded. MRI scans for repeat treatments were fused with initial SRS plan. New lesions were outlined on the initial SRS planning CT. The mean dose that the site of new lesions received from initial SRS was tabulated. RESULTS: Thirty-eight patients met inclusion criteria. 165 new lesions were evaluated. There was a lower propensity to develop new brain lesions with increasing dose received by the regions from prior SRS, with 66%, 34%, 19%, 13%, 6%, 5%, 2% and 1% of new lesions appearing in regions that received less than 1 Gy, greater than or equal to 1, 2, 3, 4, 5, 6, and 7 Gy, respectively. Higher doses are received by smaller brain volumes during SRS. After accounting for volume, 14, 14, 11, 7, 2, 2, 1 and 1 new lesions appeared per 100 cm3 of brain in regions that received doses of less than 1 Gy, greater than or equal to 1, 2, 3, 4, 5, 6, and 7 Gy, respectively, from prior SRS. CONCLUSIONS: We identified low dose spillage during SRS to be associated with lower incidence of new brain metastases. Validation in larger dataset or prospective study of the combination of SRS with low dose WBRT would be crucial in order to establish causality of these findings.

Proton Therapy for Partial Breast Irradiation: Rationale and Considerations.

In an era of continued advancements in personalized medicine for the treatment of breast cancer, select patients with early stage breast cancer may be uniquely poised to benefit from partial breast irradiation (PBI) delivered with proton therapy. PBI presents an opportunity to improve quality of life during treatment with a significantly shorter treatment duration. By targeting less non-target breast tissue, excess radiation exposure and resulting toxicities are also reduced. Proton therapy represents a precision radiotherapy technology that builds on these advantages by further limiting the normal tissue exposure to unnecessary radiation dose not only to uninvolved breast tissue but also the underlying thoracic organs including the heart and lungs. Herein, we present a concise review of the rationale for the use of proton therapy for PBI, evidence available to date, and practical considerations in the implementation and use of proton therapy for this indication.

Prevention of Breast Cancer-Related Lymphedema.

Tremendous progress has been made over the past several decades in the treatment of breast cancer. Mortality and recurrence rates continue to decline. Our ability to tailor patient- and tumor-specific treatments has rapidly advanced. The vast majority of our patients can safely have breast conservation. Unfortunately, for many patients, survivorship is burdened by ongoing quality-of-life issues. Most breast cancer patients are asymptomatic at presentation, and the onus is on us to preserve this. Surgery, radiation, and systemic therapy can result in long-term toxicities that can be amplified with multimodality approaches. We must strive to apply minimally effective therapies rather than a maximally tolerated approach. Breast cancer-related lymphedema (BCRL) is a particularly dreaded chronic complication. This review strives to give the reader a better understanding of BCRL and shed light on wisely choosing an integration of treatment modalities that minimizes BCRL risk. Key literature on emerging concepts is highlighted.

Prolongation of radiotherapy duration is associated with inferior overall survival in patients with pediatric medulloblastoma and central nervous system primitive neuroectodermal tumors.

BACKGROUND: The importance of radiotherapy (RT) duration in medulloblastoma in the modern era of chemotherapy has not been well elucidated. The aim of this study was to determine the impact of RT treatment duration on overall survival (OS) in pediatric medulloblastoma and cenral nervous system neuroectodermal tumors (PNETs). METHODS: The National Cancer Database (NCDB) was queried to identify patients with newly diagnosed medulloblastoma and CNS PNETs diagnosed between 2004 and 2014. Patients were excluded if they had extraneural metastasis, did not receive standard craniospinal irradiation dose, had a nonstandard total dose outside of 54 or 55.8 Gy, did not receive adjuvant chemotherapy, or if the RT duration was outside of the expected range of 37 to 80 days. The Kaplan-Meier estimator was used to estimate the association between RT duration (≤45 days or >45 days) and OS. Multivariate Cox regression was used to assess other confounders of OS. RESULTS: Six-hundred twenty-five patients met inclusion criteria, of which 181 were assigned to the "RT long" (>45 days) cohort (29.0%) and 444 (71.0%) to the "RT short" group (≤45 days). The five-year OS for the "RT short" compared with "RT long" cohort was 82.2% versus 70.9%, respectively (log-rank, P < 0.0037). For average risk patients, the five-year OS was 84.6% versus 86.4% for "RT short" and "RT long," respectively (log-rank, P = 0.40). However, for high-risk patients, five-year OS was 77.7% versus 51.0% (log-rank, P < 0.0001) in the "RT short" and "RT long" cohorts. CONCLUSION: For patients with high-risk medulloblastoma and CNS PNETs, RT duration >45 days was associated with inferior OS.

Potential Mechanisms of Cancer-Related Hypercoagulability.

The association between cancer and thrombosis has been known for over a century and a half. However, the mechanisms that underlie this correlation are not fully characterized. Hypercoagulability in cancer patients can be classified into two main categories: Type I and Type II. Type I occurs when the balance of endogenous heparin production and degradation is disturbed, with increased degradation of endogenous heparin by tumor-secreted heparanase. Type II hypercoagulability includes all the other etiologies, with factors related to the patient, the tumor, and/or the treatment. Patients with poor performance status are at higher risk of venous thromboembolism (VTE). Tumors can result in VTE through direct pressure on blood vessels, resulting in stasis. Several medications for cancer are correlated with a high risk of thrombosis. These include hormonal therapy (e.g., tamoxifen), chemotherapy (e.g., cisplatin, thalidomide and asparaginase), molecular targeted therapy (e.g., lenvatinib, osimertinib), and anti-angiogenesis monoclonal antibodies (e.g., bevacizumab and ramucirumab).

A Novel Tripod Percutaneous Reconstruction Technique in Periacetabular Lesions Caused by Metastatic Cancer.

BACKGROUND: Metastatic lesions in the periacetabular region can cause pain and immobility. Symptomatic patients are often treated surgically with a total hip replacement using various modified Harrington methods. These open surgical procedures confer inherent risks. Prolonged recovery and potential complications may delay adjuvant radiation and systemic therapy. METHODS: We describe a novel technique for acetabular reconstruction. Three large-bore cannulated screws are placed percutaneously under fluoroscopy in a tripod configuration to reinforce the mechanical axes of the acetabulum. Increased stability improves pain control and permits weight-bearing. RESULTS: Twenty consecutive patients with periacetabular metastases were treated using the tripod technique. Eighteen patients (90%) had Harrington class-III lesions, and 2 patients had Harrington class-II lesions. The mean surgical time was 2.3 hours. Sixteen patients (80%) were able to get out of bed on postoperative day 1. At 3 months postoperatively, there was significant improvement in pain as documented on their visual analog scale (p < 0.01) and in functionality as measured by the Eastern Cooperative Oncology Group score (p < 0.01). The mean follow-up time was 7 months (range, 0.6 to 20 months). At the most recent follow-up, only 3 among the 16 surviving patients were using opioids chronically for pain. Total hip arthroplasty was performed in 4 patients (20%) in a staged fashion using the previously placed screws as support for a cemented cup and obviating the need for a cage device. Of the 16 patients, 15 could walk either independently (6 patients) or using an ambulatory aid (9 patients). Eight patients with the primary tripod reconstruction survived >6 months postoperatively. They were found to have either new bone formation filling the defects or healing of the pathological fractures. There has been no implant loosening or failure. CONCLUSIONS: The tripod technique is a novel application to provide safe and effective pain relief in the context of periacetabular metastatic disease. It can be easily converted to support a cemented acetabular cup for a total hip replacement should disease progression occur. This technique provides an alternative to open surgery as currently practiced in these patients. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Comparison of Local Recurrence Risk Estimates After Breast-Conserving Surgery for DCIS: DCIS Nomogram Versus Refined Oncotype DX Breast DCIS Score.

BACKGROUND: A ductal carcinoma in situ (DCIS) Nomogram integrating 10 clinicopathologic/treatment factors and a Refined DCIS Score (RDS) that incorporates a genomic assay and three clinicopathologic factors (Oncotype DX DCIS Score) are available to estimate DCIS 10-year local recurrence risk (LRR). This study compared these estimates. METHODS: Patients 50 years of age or older with DCIS size 2.5 cm or smaller and a genomic assay available were identified. An RDS within 1-2% of the range of Nomogram LRR estimates obtained by assuming use and non-use of endocrine therapy (Nomogram ± ET) was defined as concordant. Assuming a 10-year risk threshold of 10% for recommending radiation, Nomogram ± ET and RDS estimates were compared, and threshold concordance was determined. RESULTS: For 54 (92%) of 59 patients, the RDS and Nomogram ± ET LRR estimates were concordant. For the remaining 5 (8%) of the 59 patients, the RDS LRR estimates were lower than the Nomogram + ET estimates, with an absolute difference of 3-8%, and thus were discordant. For these five patients, the RDS estimates of 10-year LRR were lower than 10% (range 5-8%) and the Nomogram + ET estimates were 10% or higher (range 11-14%). These five patients with both discordant and threshold-discordant estimates all had close margins (≤ 2 mm). CONCLUSIONS: Among 92% of women 50 years of age or older with DCIS size 2.5 cm or smaller, free-of-charge online Nomogram 10-year LRR estimates were concordant with those obtained using the commercially available RDS (> $4600). Among the 8% with discordant risk estimates, the RDS appeared to underestimate the LRR and may lead to inappropriate omission of radiotherapy. Unless other data show a clinically significant advantage of the RDS (Oncotype DX DCIS Score), the study data suggest that for women 50 years of age or older with DCIS size 2.5 cm or smaller, its use is not warranted.