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.

Radiotherapy Combined with Raltitrexed and Irinotecan for Treating Unresectable Recurrent Colorectal Cancer

Background:Locally recurrent colorectal cancer is often associated with considerable morbidity and poor quality of life. Moreover, surgical resection is frequently not viable because of tumor fixation in the pelvis. This study aimed to evaluate the effects and safety of intensity-modulated radiotherapy when administered concurrently with raltitrexed and irinotecan to patients with unresectable recurrent colorectal cancer.Methods:Eligible patients had unresectable pelvic recurrence of colorectal cancer, UGT1A1 genotype *1*1 or *1*28, and were refractory to, or intolerant of, chemotherapy with fluoropyrimidine and oxaliplatin. Intensity-modulated radiation therapy (IMRT) was delivered to the pelvis with a total dose of 50–60 Gy in 25–30 fractions, concurrently with irinotecan (200 mg/m2 on days 1 and 22) and raltitrexed (3 mg/m2 on days 1 and 22). After completion of radiation treatment, patients underwent surgery or continued the same regimen of chemotherapy and were assessed by a multidisciplinary team. The primary endpoint was the objective response rate, evaluated using RECIST version 1.1. Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), local progression-free survival (LPFS), and safety. Clinical and imaging evaluations were scheduled every month during treatment.Results:Between January 1, 2019, and July 14, 2020, 30 patients were enrolled in this study at the Fudan University Shanghai Cancer Center. All patients completed radiotherapy with a median number of 5 chemotherapy cycles (range, 2–10). Twelve patients (40%) experienced an objective response, including two complete responses and ten partial responses. Seventeen patients exhibited stable disease, leading to a DCR of 96.7%. With a median follow-up of 13 (range, 4–25) months, progression was observed in 20 patients (11 loco-regional failures, 11 distant metastases, and 5 deaths). The median PFS was 13 (95% confidence interval [CI], 9–18) months; the median LPFS was 15 (95% CI, 14 to not reached) months. The incidence of grade 3 or 4 adverse events was 26.7%. The most common grade 3 or 4 adverse event was neutropenia (13.3%).Conclusions:IMRT with concurrent raltitrexed and irinotecan exhibited encouraging efficacy with an acceptable toxicity profile in patients with unresectable recurrent colorectal cancer.Trial registration: ClinicalTrials.gov: NCT04499586, registered on July 31, 2020 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04499586.

MET-8 Chemotherapy alone for brain metastases from small cell lung cancer -comparison with EGFR-TKI-

Background: Because of the invasive nature of small cell lung cancer (SCLC), the effectiveness of local therapy for brain metastases (BM) from SCLC had been limited. In this article, we retrospectively evaluated the efficacy of chemotherapy against non-treated BM from SCLC (SCLC-CHT) in compared with TKI for BM from EGFR-mutated NSCLC (EGFR-TKI).Materials and Methods: Un-treated 218 BM, including 58 SCLCs and 160 EGFR-mutated NSCLCs were enrolled. The primary endpoints were maximum response of BM and the duration of effect, and the secondary endpoints were times to the first and maximum responses, patterns of progression and overall survival after the diagnosis of BM.Results: The objective response rate (69%) and disease control rate (92%) of BM after SCLC-CHT were inferior to those after EGFR-TKI (85%, 97%), but were sufficiently satisfactory. Both the times to the first response (0.8m, 95% CI:0.6–0.9) and to the maximum effect after treatment(1.6m, 0.9–1.9) with SCLC-CHT were shorter than with EGFR-TKI (0.9m,0.9–1.0, P=0.011, and 2.4m, 1.9–2.8, P=0.004), but the duration of the response was conversely shorter with SCLC-CHT (5.1m, 4.2–5.6) than with EGFR-TKI (12.3m,9.2–15.1, P<0.0001). The dominant pattern of recurrence was local progression in the both groups. The risk of local progression after SCLC-CHT was higher than after EGFR-TKI (Fine-Gray HR:2.44, 1.56–3.83, P<0.0001), although the risk of new BM was not different between these two groups (0.94, 0.49–1.82, P=0.86). The risk of non-CNS death was higher after SCLC-CHT than after EGFR-TKI (1.8, 1.2–2.7, P=0.004), but the risk of CNS death was not different (0.92, 0.45–1.89,P=0.83).Conclusions: BM from SCLC well and quickly responded to CHT, but the duration of response was short. These responses of BM against CHT was comparable to that of extracranial disease. For the better control of BM and survival of patients, ingenuity to prolong the effect of CHT is required.

A phase II study of laser interstitial thermal therapy combined with doxorubicin in patients with recurrent glioblastoma

Background The blood brain barrier (BBB) is a major limiting factor for drug delivery in brain tumors. Laser interstitial thermal therapy (LITT) disrupts the peritumoral BBB. In this study, we examine survival in patients with recurrent glioblastoma (GBM) treated with LITT followed by low-dose doxorubicin, a potent anti-neoplastic drug with poor BBB permeability. Methods Forty-one patients with recurrent GBM were enrolled; thirty patients were evaluable. Participants underwent LITT followed by 6 weekly doxorubicin treatments starting within one week (Early Arm) or at 6-8 weeks (Late Arm) after LITT. The overall survival (OS), local progression-free survival (PFS), and any PFS were compared to historical controls treated with bevacizumab salvage therapy (n = 50) or LITT with standard BBB-permeable salvage therapy (n = 28). Cox proportional hazards models examined the contribution of age, gender, MGMT promoter status, and IDH-mutation status on any PFS and OS. Adverse events were also cataloged. Results The Late Arm and all patients (Early Arm + Late Arm) demonstrated significant improvement in OS compared to historical controls treated with bevacizumab (p < 0.001) and LITT with standard salvage therapy (p < 0.05). No significant difference in any PFS was observed between either arm and historical controls. Low-dose doxorubicin was well-tolerated with comparable adverse event rates between the arms. Conclusions Low-dose doxorubicin given after LITT is well tolerated and correlated with higher OS compared to historical controls treated with bevacizumab or LITT with standard salvage chemotherapy. A larger study is needed to further characterize survival and progression patterns.

Clinical Effectiveness of Hypofractionated Proton Beam Therapy for Liver Metastasis From Breast Cancer

BackgroundFew studies of proton beam therapy (PBT) for patients with liver metastasis from breast cancer (LMBC) are available to date. The aim of the present study was to evaluate the clinical effectiveness of PBT for patients with LMBC.Material and MethodsSeventeen patients with LMBC treated with PBT were included in this study. The median prescribed dose of PBT was 66 GyE (range, 60–80) in 10 fractions, 5 times a week. In patients with LMBC receiving PBT, freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) rates were assessed.ResultsThe median follow-up time was 34.2 months (range, 11.5–56.1). The median FFLP time was not yet reached, and the 3-year FFLP rates were 94.1% (95% confidence interval [CI], 82.9–105.3). The median times of PFS and OS were 7.9 months (95% CI, 5.3–10.5) and 39.3 months (95% CI, 33.2–51.9), respectively, and the 3-year PFS and OS rates were 19.6% (95% CI, -1.8–41.0) and 71.7% (95% CI, 46.8–96.6), respectively. Grade 3 or higher adverse events were not observed.ConclusionPBT for patients with LMBC showed promising FFLP and OS with safe toxicity profiles. These findings suggest that PBT can be considered a local treatment option in patients with LMBC.

Prospective comparative study of intraoperative balloon electronic brachytherapy versus resection with multidisciplinary adjuvant therapy for recurrent glioblastoma

Background: Intraoperative balloon electronic brachytherapy (IBEB) may provide potential benefit for local control of recurrent cerebral glioblastomas (GBMs). Methods: This is a preliminary report of an open-label, prospective, comparative cohort study conducted in two neurosurgical centers with ongoing follow-up. At recurrence, patients at one center (n = 15) underwent reresection with IBEB while, at the second center (n = 15), control subjects underwent re-resection with various accepted second-line adjuvant chemoradiotherapy options. A comparative analysis of overall survival (OS) and local progression-free survival (LPFS) following re-resection was performed. Exploratory subgroup analysis based on postoperative residual contrast-enhanced volume status was also done. Results: In the IBEB group, median LPFS after re-resection was significantly longer than in the control group (8.0 vs. 6.0 months; log rank χ2 = 4.93, P = 0.026, P < 0.05). In addition, the median OS after second resection in the IBEB group was also significantly longer than in the control group (11.0 vs. 8.0 months; log rank χ2 = 4.23, P = 0.04, P < 0.05). Conclusion: These hypothesis-generating results from a small cohort of subjects suggest putative clinical benefit in OS and LPFS associated with maximal safe re-resection of recurrent GBM with IBEB versus re-resection and standard adjuvant therapy, a hypothesis that deserves further testing in an appropriately powered clinical trial.

Glioblastoma Multiforme In The Pineal Region: Systematic Review Of The Survival Outcomes

Purpose: Glioblastoma multiforme of the pineal region harbors high mortality in the first year of treatment. This study aims to deepen the study of pineal GBM patients for finding independent predictors of mortality, focusing on the therapeutic modalities and genetic features.Methods: We present a systematic review of the long-term outcomes of the disease with a focus on the therapeutic modalities and genetic features.Results: The median overall survival of the disease is 12 months. Biopsy (HR:4.2, p=0.002, and a median survival of 19 months) and radiochemotherapy (HR:4.1, p<0.001, and a median survival of 18 months) represent independent predictors of pineal glioblastoma survival. H3K27M mutant patients had a median survival of 23 months versus the ten-months median survival of the H3K27 wild type. However, no statistical difference exists due to the limited number of cases. The disease's local progression and recurrence seem higher in patients undergoing surgical removal than biopsy procedures (p=0.021).Conclusions: Biopsy and radiochemotherapy represent independent predictors of pineal GBM survival. Surgical resection different from biopsy seems to increase the risks of local progression and recurrence. However, further studies should focus on the impact of the genetic profile on long-term outcomes.

Excellent Response to Very Low Dose Radiation (4Gy) For Indolent B-cell Lymphomas: Is 4Gy Suitable for Curable Patients?

Radiotherapy plays an important role in managing highly radiosensitive, indolent non-Hodgkin lymphomas (iNHL), such as follicular lymphoma (FL) and marginal zone lymphoma (MZL). While the standard of care for localized iNHL remains 24Gy, de-escalation to very low dose radiotherapy (VLDRT) of 4Gy further reduces toxicities and treatment duration. Use of VLDRT outside of palliative indications remains controversial, however, we hypothesize that it may be sufficient for most lesions. We present the largest single institution VLDRT experience of adult patients with FL and MZL treated between 2005 and 2018 (n=299 lesions; 250 patients) utilizing modern principles including PET staging and involved site radiotherapy (ISRT). Outcomes include best clinical/radiographic response between 1.5-6 months post-VLDRT, and cumulative incidence of local progression (LP) with only death as competing risk. Post-VLDRT, the overall response rate was 90% for all treated sites with 68% achieving complete response (CR). With median follow-up of 2.4 years, the 2-year cumulative incidence of LP was 25% for the entire cohort and 9% after frontline VLDRT treatment for potentially curable, localized disease. Lesion size &gt;6cm was associated with lower odds of attaining a CR and greater risk of LP. There was no suggestion of inferior outcomes for potentially curable lesions. Given the clinical versatility of VLDRT, we propose to implement a novel, incremental, adaptive ISRT strategy where patients will be treated initially with VLDRT, reserving full dose treatment for those who fail to attain a CR.