Stereotactic Radiation and Dual Human Epidermal Growth Factor Receptor 2 Blockade with Trastuzumab and Pertuzumab in the Treatment of Breast Cancer Brain Metastases: A Single Institution Series.

(1) Background: This study aims to assess the safety and efficacy of fractionated SRT (fSRT) and pertuzumab-trastuzumab (PT) in patients with breast cancer brain metastases (BCBM). (2) Methods: Patients with HER2+ BCBM who received FSRT from 2015 to 2019 were identified. Patients were included if they were treated with fSRT within 21 days of receiving PT. All lesions were treated with LINAC-based fSRT to a total dose of 27 Gy delivered in three consecutive fractions. All patients received concurrent PT. Patients were evaluated 4-6 weeks after SRS and subsequently every 2-3 months with MRI re-imaging (3) Results: A total of 49 patients with HER2+ brain metastases were identified. Of these patients, a total of 10 patients with 32 HER2+ BCBM were treated with concurrent SRT and PT and included in the analysis. No local progression was observed. Overall response rate was 68.7%. Only one patient developed asymptomatic radionecrosis. Median time to BM occurrence was 15.6 (range: 1-40.5 months). Distant intracranial failure occurred in 4/10 patients (40.0%). Overall BCBM median survival was 33.9 months (95%CI 24.1-43.6). Mean duration of PT treatment was 27.9 months (range: 10.1-53.7 months). (4) Conclusions: In our single institution experience, fSRT and PT showed to be a safe treatment for patients with BCBM with an adequate overall response rate.

Long-Term Results of a Prospective Phase 2 Study on Volume De-Escalation in Neoadjuvant Chemoradiotherapy of Rectal Cancer.

PURPOSE: In the current study, we evaluated whether neoadjuvant chemoradiotherapy with reduced treatment volumes due to the exclusion of elective pelvic nodal irradiation is a feasible strategy for selected patients with locally advanced rectal cancer. METHODS AND MATERIALS: Patients with T2 low-lying/T3, N0-N1 rectal lesions without evidence of disease in the lateral lymph nodes were prospectively recruited. All patients underwent pretreatment testing, including computed tomography imaging of the chest, abdomen, and pelvis with intravenous contrast, pelvic magnetic resonance imaging with intravenous contrast, and 18-fluorodeoxyglucose positron emission/computed tomography. The clinical target volume included the primary tumor and the mesorectum with vascular supply containing the perirectal and presacral nodes, with the upper border at the S2/S3 interspace. The total radiation dose was 50.4 Gy, and fluoropyrimidine-based chemotherapy was associated concomitantly. The primary endpoint of the study was the reduction of gastrointestinal (GI) toxicity, and the secondary endpoints were pathologic complete response, local control, overall survival, and disease-free survival. RESULTS: Fifty-two patients (30 men, 22 women) with a median age of 67 years (range, 45-85 years) were enrolled in the study. Acute grade 3 GI toxicity was 7.6%, and there were no cases of grade 4 toxicity. Three patients (5.7%) developed a local recurrence. No relapse occurred in the lateral lymph nodes. The local control rate at 5 years was 96.1%. With a median follow-up time of 72.9 months (range, 2.5-127.6 months), the 3- and 5-year overall survival rates were 89.4% and 87%, respectively. The 3- and 5-year disease-free survival rates were 82.4% and 82.4%, respectively. CONCLUSIONS: De-escalation of radiation therapy target volume reduces GI side effects without compromising efficacy in patients with rectal cancer. These results cannot be clearly extended to high-risk disease and need further evaluation in future randomized trials.

Efficacy of a Propolis-Based Syrup (FARINGEL) in Preventing Radiation-Induced Esophagitis in Locally Advanced Lung Cancer.

AIM: To evaluate the efficacy of a propolis-based syrup, FARINGEL®, in preventing radiation-induced esophagitis in locally advanced lung cancer patients. METHODS: Patients were treated with concurrent chemoradiotherapy (CRT) using involved-field radiotherapy (RT). Every patient received FARINGEL at the beginning of CRT until the first follow-up. The data of the study group were compared with the data of a control group treated without the administration of the syrup. RESULTS: Forty-five patients were enrolled. Forty-one (91.1%) completed the protocol and were evaluable for esophagitis. Grade ≥2 toxicity occurred in 9/41 patients (22%). No differences in overall toxicity were detected between the study group and the control group (n = 55, 60.9 vs. 54.5%; p = ns). Grade 2-3 esophagitis was lower in the study group in comparison with the control group (22 and 38%, respectively), but statistical significance was not reached (p = 0.09). However, the onset of grade ≥2 esophagitis was delayed in the study group compared to the control group, occurring at higher doses of RT (41.8 vs. 25.4 Gy; p < 0.001). Furthermore, the mean number of interruption days for esophagitis was lower in the study group than in the control group (0.6 ± 2.0 vs. 2.1 ± 3.6; p = 0.025). CONCLUSION: FARINGEL was well-tolerated and delayed esophagitis that was induced by CRT for locally advanced lung cancer.

Phase II study of induction chemotherapy followed by chemoradiotherapy in patients with borderline resectable and unresectable locally advanced pancreatic cancer.

There is not a clear consensus regarding the optimal treatment of locally advanced pancreatic disease. There is a potential role for neoadjuvant therapy to treat micrometastatic disease with chemotherapy, as well as for the treatment of local disease with radiotherapy. We evaluated the safety and efficacy of induction chemotherapy with oxaliplatin and gemcitabine followed by a high weekly dose of gemcitabine concurrent to radiation therapy in patients with borderline resectable and unresectable locally advanced pancreatic cancer. In our study, 41 patients with pancreatic cancer were evaluated. In all cases an accurate pre-treatment staging was performed. Patients with evidence of metastatic disease were excluded, and thus a total of 34 patients were consequently enrolled. Of these, twenty-seven patients (80%) had locally advanced unresectable tumours, seven patients (20%) had borderline resectable disease. This protocol treatment represents a well-tolerated promising approach. Fifteen patients (55.5%) underwent surgical radical resection. With a median follow-up of 20 months, the median PFS and OS were 20 months and 19.2 months, respectively. The median OS for borderline resectable patients was 21.5 months compared with 14 months for unresectable patients (p = 0.3). Continued optimization in multimodality therapy and an accurate patient selection remain crucial points for the appropriate treatment of these patients.

Prospective study of cetuximab and gemcitabine in combination with radiation therapy: feasibility and efficacy in locally advanced pancreatic head cancer.

BACKGROUND: Radio-chemotherapy is one of the steps of multidisciplinary management in locally advanced pancreatic cancer. The Epidermal Growth Factor Receptor (EGFR) plays an important role in the disease pathway. The purpose of this prospective study is to evaluate the feasibility and the efficacy of radiotherapy in combination with gemcitabine and EGFR targeting therapy for patients with locally advanced disease. MATERIALS AND METHODS: From November 2008 through January 2012, 34 patients were included in this study. In all cases an accurate pre-treatment staging including CT scan, Endoscopic Ultra-Sonography (EUS), 18F - fluorodeoxyglucose (18F-FDG) PET-CT and laparoscopy with peritoneal washing was performed. External beam radiation was delivered with a total dose of 50.4 Gy (1.8 Gy per fraction). Patients were treated using 3D- conformal radiotherapy, and the clinical target volume was the primary tumor and involved lymph nodes. Gemcitabine 300 mg/m(2) and Cetuximab were given weekly during radiation therapy. RESULTS: Ten patients (29.4 %) were excluded from the protocol because of the evidence of metastatic disease at the pre-treatment staging. Three patients refused radiochemotherapy. Twenty-one patients completed the therapy protocol. During the combined therapy grade 3-4 toxicities observed were only haematological (leukopenia 47,6 %, trombocytopenia 4.8 %, elevated gamma-GT 23.8 %, elevated alkaline phosphatase 4,8 %). Non-haematological toxicity grade 3-4 was never reported. Post-treatment workup showed partial response in five patients (24 %), stable disease in 11 patients (52 %) and disease progression in 5 patients (24 %). Two-year Local Control was 49 % (median, 18.6 months), 2-year Metastases Free Survival was 24 % (median, 10.8 months). One and two-year Overall Survival were 66 % and 28 % respectively, with a median survival time of 15.3 months. CONCLUSIONS: The combination of cetuximab and gemcitabine with concurrent radiation therapy provides a feasible and well tolerated treatment for locally advanced pancreatic cancer. Patients' selection is crucial in order to treat patients appropriately.

The role of mammography after breast-conserving surgery and adjuvant chemotherapy.

AIMS AND BACKGROUND: To investigate the impact of postchemotherapy mammography on radiotherapy timing and detection of early locoregional recurrences in breast cancer patients treated with breast-conserving surgery and adjuvant chemotherapy. METHODS: Bilateral mammography was performed before radiotherapy. Mammogram assessments were collected using the Breast Imaging Reporting and Data System (BI-RADS) scale. Differences in waiting times for radiotherapy between patients who needed further evaluation after mammograms and who did not were tested by the nonparametric Mann-Whitney U test. RESULTS: A total of 277 patients who underwent locoregional restaging after conservative surgery and adjuvant chemotherapy were evaluated. All patients had surgical margins greater than 2 mm. No locoregional recurrences were detected. Only in 2 patients (0.7%) did preradiotherapy mammograms reveal a contralateral breast cancer, which was histologically confirmed. After chemotherapy, the waiting times for radiotherapy were not different between patients who needed further imaging evaluation and patients who did not (34 days, 95% CI: 29-65 vs 38 days, 95% CI: 32-39; P = NS). CONCLUSION: According to these data, postchemotherapy mammography detected a contralateral breast cancer in very few cases (0.7%); thus, even if performing these exams did not delay the start of radiotherapy, we believe that preradiotherapy mammograms are not necessary for patients undergoing adjuvant chemotherapy after breast-conserving surgery.