Rate of pachymeningeal failure following adjuvant WBRT vs SRS in patients with brain metastases.

Background: Stereotactic radiosurgery (SRS) has supplanted whole brain radiotherapy (WBRT) as standard-of-care adjuvant treatment following surgery for brain metastasis (BrM). Concomitant with the adoption of adjuvant SRS, a new pattern of failure termed "Pachymeningeal failure" (PMF) has emerged. Methods: We reviewed a prospective registry of 264 BrM patients; 145 and 119 were treated adjuvantly with WBRT and SRS, respectively. The Cox proportional hazards model was used to identify variables correlating to outcomes. Outcomes were calculated using the cumulative incidence (CI) method. Univariate (UVA) and multivariate analyses (MVA) were done to identify factors associated with PMF. Results: CI of PMF was 2 % and 18 % at 12 months, and 2 % and 23 % at 24 months for WRBT and SRS, respectively (p < 0.001). The CI of classic leptomeningeal disease (LMD) was 3 % and 4 % at 12 months, and 6 % and 6 % at 24 months for WBRT and SRS, respectively (P = 0.67). On UVA, adjuvant SRS [HR 9.75 (3.43-27.68) (P < 0.001)]; preoperative dural contact (PDC) [HR 6.78 (1.64-28.10) (P = 0.008)]; GPA score [HR 1.64 (1.11-2.42) (P = 0.012)]; and lung EGFR/ALK status [HR 3.11 (1.02-9.45) (P = 0.045)]; were associated with PMF risk. On MVA, adjuvant SRS [HR 8.15 (2.69-24.7) (P < 0.001)]; and PDC [HR 6.28 (1.51-26.1) (P = 0.012)] remained associated with PMF. Conclusions: Preoperative dural contact and adjuvant SRS instead of adjuvant WBRT were associated with an increased risk of PMF. Strategies to improve pachymeningeal radiation coverage to sterilize at risk pachymeninges should be investigated.

Locoregional Ablative Radiation Therapy for Patients With Breast Cancer Unsuitable for Surgical Resection.

PURPOSE: Patients with breast cancer who are unsuitable for surgical resection are typically managed with palliative systemic therapy alone. We report outcomes of 5-fraction ablative radiation therapy for nonresected breast cancers. METHODS AND MATERIALS: This is a retrospective analysis of an institutional registry of patients with breast cancer who were unsuitable for resection and underwent 35 to 40 Gy/5 fractions to the primary breast tumor or regional lymph nodes from 2014 to 2021. Primary outcomes were cumulative incidence of local failure and grade ≥3 toxicity (Common Terminology Criteria for Adverse Events, version 5.0). RESULTS: We reviewed 57 patients who received 61 treatment courses (median age of 81 years; range, 38-99). Unresectable tumor (10%), patient refusal (18%), medical inoperability (35%), and metastatic disease (37%) were the causes of not having surgery. Five patients (8%) had previously undergone adjuvant locoregional radiation therapy. Fifty-four percent (n = 33/61) of treatment courses targeted the breast only, 31% (n = 19/61) both the breast and lymph nodes, and 15% (n = 9/61) the lymph nodes only. Sixty-seven percent (n = 35/52) of the courses that targeted the breast were delivered with partial breast irradiation and 33% (n = 17/52) with whole breast radiation therapy (median dose of 25 Gy in 5 fractions) ± simultaneous integrated boost to the primary tumor. Most primary tumors (65%, n = 34/52) and target lymph nodes (61%, n = 17/28) were treated with a dose of 35 Gy in 5 fractions. Most treatments (52%) were delivered with intensity modulated radiation therapy (IMRT). Radiation therapy was delivered daily (20%), every other day (18%), twice weekly (36%), or weekly (26%). The 2-year cumulative incidence of local failure was 11.4% and grade≥3 toxicity was 15.1%. The grade ≥3 toxicity was 6.5% for IMRT treatments, versus 7.7% for non-IMRT treatments targeting partial breast or lymph nodes (hazard ratio, 1.13, P = .92), versus 38.9% for non-IMRT treatments targeting the entire breast (hazard ratio, 6.91, P = .023). All grade ≥3 toxicity cases were radiation dermatitis. No cases of brachial plexopathy were observed. CONCLUSIONS: Thirty-five to 40 Gy in 5 fractions is a safe and effective breast stereotactic body radiation therapy (SBRT) regimen and may be an attractive option for patients who are not surgical candidates. Highly conformal techniques (ie, IMRT or partial breast irradiation) were associated with a reduced risk of toxicity and should be the preferred treatment approaches.

Retrospective analysis of VES-13 questionnaires in the Senior Women's Breast Cancer Clinic at Sunnybrook Health Sciences, Toronto, Ontario, Canada.

PURPOSE: Vulnerable Elder Survey (VES-13) is a screening tool used in assessing older vulnerable patients at risk of functional decline. We sought to evaluate how VES-13 tool would impact oncologist referral pattern to geriatricians as our primary outcome. We also sought to better understand how VES-13 scores impacted referral to additional services (allied healthcare), and modification to oncological treatment. METHODS: A retrospective review of VES-13 questionnaires completed by older women (age 70 or older) with breast cancer referred to the Senior Women's Breast Cancer Clinic (SWBCC) was undertaken. Patients with a VES-13 score of three or greater, who were at significantly higher risk of functional decline, had further retrospective chart review for risk factors that would contribute to functional decline such as Eastern Cooperative Oncology Group (ECOG) score, social supports, and current living situation. The primary and secondary endpoints described above were analyzed through bivariate comparisons and multivariable logistical regression to determine if there was any statistical significance (p < 0.05). RESULTS: 701 patients completed VES-13 form, of which 235 (33.5%) had a VES-13 score of three or greater. Less than 5% of oncologists documented VES-13 scores in their notes, with less than 5% of patients being referred for geriatric services. Neither VES-13 (p= 0.900) nor ECOG (p= 0.424) were associated with referral for geriatrics assessment. Referral to allied healthcare services was significantly associated with (ECOG) score (OR 2.24 [1.49-3.37], p < 0.0001), while not significantly associated with VES-13 score (OR 0.89 [0.78-1.02], p= 0.102). VES-13 (OR 1.23 [1.04-1.45], p=0.014) and ECOG (OR 2.37 [1.29-4.37), p=0.005) were both associated with modification in oncology treatment (chemotherapy or radiation). CONCLUSION: Approximately one third of our population was at risk of functional decline. VES-13 scores were infrequently mentioned in oncologists notes from their clinical assessments, with very few patients being referred for geriatric assessment. By not collecting and analyzing VES-13 scores, and relying on performance status alone, there is a missed opportunity in assessing for functional decline and reducing potential complications from treatment for our patients.

Study of Alteplase for Respiratory Failure in SARS-CoV-2 COVID-19: A Vanguard Multicenter, Rapidly Adaptive, Pragmatic, Randomized Controlled Trial.

BACKGROUND: Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients. RESEARCH QUESTION: Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe? STUDY DESIGN AND METHODS: Adults with COVID-19-induced respiratory failure were randomized from May14, 2020 through March 3, 2021, in two phases. Phase 1 (n = 36) comprised a control group (standard-of-care treatment) vs a tPA bolus (50-mg tPA IV bolus followed by 7 days of heparin; goal activated partial thromboplastin time [aPTT], 60-80 s) group. Phase 2 (n = 14) comprised a control group vs a tPA drip (50-mg tPA IV bolus, followed by tPA drip 2 mg/h plus heparin 500 units/h over 24 h, then heparin to maintain aPTT of 60-80 s for 7 days) group. Patients were excluded from enrollment if they had not undergone a neurologic examination or cross-sectional brain imaging within the previous 4.5 h to rule out stroke and potential for hemorrhagic conversion. The primary outcome was Pao2 to Fio2 ratio improvement from baseline at 48 h after randomization. Secondary outcomes included Pao2 to Fio2 ratio improvement of > 50% or Pao2 to Fio2 ratio of ≥ 200 at 48 h (composite outcome), ventilator-free days (VFD), and mortality. RESULTS: Fifty patients were randomized: 17 in the control group and 19 in the tPA bolus group in phase 1 and eight in the control group and six in the tPA drip group in phase 2. No severe bleeding events occurred. In the tPA bolus group, the Pao2 to Fio2 ratio values were significantly (P < .017) higher than baseline at 6 through 168 h after randomization; the control group showed no significant improvements. Among patients receiving a tPA bolus, the percent change of Pao2 to Fio2 ratio at 48 h (16.9% control [interquartile range (IQR), -8.3% to 36.8%] vs 29.8% tPA bolus [IQR, 4.5%-88.7%]; P = .11), the composite outcome (11.8% vs 47.4%; P = .03), VFD (0.0 [IQR, 0.0-9.0] vs 12.0 [IQR, 0.0-19.0]; P = .11), and in-hospital mortality (41.2% vs 21.1%; P = .19) did not reach statistically significant differences when compared with those of control participants. The patients who received a tPA drip did not experience benefit. INTERPRETATION: The combination of tPA bolus plus heparin is safe in severe COVID-19 respiratory failure. A phase 3 study is warranted given the improvements in oxygenation and promising observations in VFD and mortality. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04357730; URL: www. CLINICALTRIALS: gov.

Acute Toxicity and Local Response using Three Fractions of High Dose Rate (HDR) Brachytherapy for Curative Treatment of Carcinoma Cervix.

To determine the acute vaginal mucosal toxicity and clinical response of cervical cancer after definitive treatment with external beam radiotherapy (EBRT) and three fractions each of 8 Fray (Gy) high dose rate intracavitary brachytherapy (HDR-BT). STUDY DESIGN: Descriptive study. PLACE AND DURATION: Radiation Oncology Section, Department of Oncology, The Aga Khan University Hospital, Karachi, Pakistan from January 2008 till December 2015. METHODOLOGY: Protocol was formulated for carcinoma cervix to complete treatment in 7 weeks. Patients were treated with chemotherapy and pelvic EBRT to a total dose of 45 Gy/25 fractions, followed by three intracavitary HDR brachytherapy fractions of 8 Gy each. Vaginal toxicity and local clinical response was assessed at the end of treatment, at 4 and 8 weeks. RESULTS: A total of 57 patients were treated with HDR brachytherapy and 49 patients were evaluated for assessment of toxicity and response. According to FIGO staging system, two had stage IB2, one had IIA, thirty-six had IIB, seven had IIIB, one had IVA disease and two had IVB with para aortic nodes. Concurrent gemcitabine and cisplatin were given to 26 (46%); whereas, 28 (49%) received concurrent cisplatin alone. Grade III acute vaginal mucosal toxicity was seen in 52 and Grade IV acute vaginal mucosal toxicity was observed in 08 patients. At completion of treatment, 40 patients had complete clinical response, at 4 weeks follow-up, complete regression of disease was found in 3 more and at 8 weeks none had clinical residual disease. CONCLUSION: This regimen of HDR brachytherapy treatments is feasible, efficacious, and well-tolerated for carcinoma cervix in a setup with cost constraints. Long term toxicity and disease control remains to be reported with longer follow-up. Key Words: Carcinoma cervix, High dose rate brachytherapy, Acute toxicity, Local response, External beam radiation therapy, Intracavitary brachytherapy.

How to become a breast cancer specialist in 2018: The point of view of the second cohort of the Certificate of Competence in Breast Cancer (CCB2).

Breast cancer (BC) is the most frequent cancer in women and the leading cause of cancer death in females worldwide. Rapid research advancements add to the complexity of treatment options for this disease. It is known that the quality of patients' care is deeply affected by healthcare professionals following these advancements. There is a growing need for academic education to increase clinical knowledge and skills of physicians treating BC patients. The certificate of Competence in Breast Cancer Program (CCB) is a Certificate in Advanced Studies (CAS) organized by the European School of Oncology in cooperation with Ulm University (Germany), which focuses on both the clinical and scientific competence required for improving quality in the management of BC patients. This paper describes the experience of the second CCB cohort (CCB2), which brought together 24 physicians from four continents who shared the common will to improve their competence and skills in BC treatment.

Hidradenocarcinoma: Five Years of Local and Systemic Control of a Rare Sweat Gland Neoplasm with Nodal Metastasis.

Hidradenocarcinoma is a rare and locally aggressive tumor rendering a poor prognosis. Furthermore, very few cases present with nodal metastasis. Diagnosing such an entity, and then differentiating it from a benign counterpart, poses a great challenge to the clinicians. There are no established treatment guidelines for the management of this disease, particularly in patients with nodal involvement. We present a case of a young male who was diagnosed with hidradenocarcinoma of the scalp, along with a neck swelling. A thorough diagnostic evaluation was done with endoscopy, pathological, and radiological investigations. He was successfully treated with resection of the scalp lesion and right-sided neck dissection followed by adjuvant concurrent chemoradiation. He remains free of any local and distant disease after five years of regular follow-up.