Radiation therapy for locally recurrent breast cancer.

Approximately one-third of all breast cancer patients experience local recurrence of their tumor after initial treatment. As initial treatment often employs the use of radiation therapy (RT), the standard of care for local breast cancer recurrence after initial breast conserving therapy has traditionally been surgical intervention with mastectomy. However, recent attempts to preserve the intact breast after recurrence with local excision have revealed a potential need for RT in addition to repeat breast conserving surgery as rates of local failure with resection alone remain high. Additionally, local recurrence following initial mastectomy and chest wall RT can be treated with reirradiation to increase local control. Repeating RT, however, in a previously irradiated area, is a complex treatment strategy, as the clinician must carefully balance maximizing treatment effectiveness while minimizing treatment-related toxicity. As a result, physicians have been hesitant to treat recurrent disease with repeat RT with limited data. Results from the current literature are promising and current clinical trials are underway to explore reirradiation modalities which will provide additional information on treatment-related toxicity and outcomes. This paper will review the current literature on repeat radiation therapy for locally recurrent breast cancer

Weekly paclitaxel, gemcitabine, and external irradiation followed by randomized farnesyl transferase inhibitor R115777 for locally advanced pancreatic cancer.

PURPOSE: The Radiation Therapy Oncology Group (RTOG) multi-institutional Phase II study 98-12, evaluating paclitaxel and concurrent radiation (RT) for locally advanced pancreatic cancer, demonstrated a median survival of 11.3 months and a 1-year survival of 43%. The purpose of the randomized Phase II study by RTOG 0020 was to evaluate the addition of weekly low- dose gemcitabine with concurrent paclitaxel/RT and to evaluate the efficacy and safety of the farnesyl transferase inhibitor R115777 following chemoradiation. PATIENTS AND METHODS: Patients with unresectable, nonmetastatic adenocarcinoma of the pancreas were eligible. Patients in Arm 1 received gemcitabine, 75 mg/m(2)/week, and paclitaxel, 40 mg/m(2)/week, for 6 weeks, with 50.4 Gy radiation (CXRT). Patients in Arm 2 received an identical chemoradiation regimen but then received maintenance R115777, 300 mg twice a day for 21 days every 28 days (CXRT+R115777), until disease progression or unacceptable toxicity. RESULTS: One hundred ninety-five patients were entered into this study, and 184 were analyzable. Grade 4 nonhematologic toxicities occurred in less than 5% of CXRT patients. The most common grade 3/4 toxicity from R115777 was myelosuppression; however, grade 3/4 hepatic, metabolic, musculoskeletal, and neurologic toxicities were also reported. The median survival time was 11.5 months and 8.9 months for the CXRT and CXRT+R115777 arms, respectively. CONCLUSIONS: The CXRT arm achieved a median survival of almost 1-year, supporting chemoradiation as an important therapeutic modality for locally advanced pancreatic cancer. Maintenance R115777 is not effective and is associated with a broad range of toxicities. These findings provide clinical evidence that inhibition of farnesylation affects many metabolic pathways, underscoring the challenge of developing an effective K-ras inhibitor

Inclusion of cGAMP within virus-like particle vaccines enhances their immunogenicity

Cyclic GMP-AMP (cGAMP) is an immunostimulatory molecule produced by cGAS that activates STING. cGAMP is an adjuvant when administered alongside antigens. cGAMP is also incorporated into enveloped virus particles during budding. Here, we investigate whether inclusion of cGAMP within viral vaccine vectors enhances their immunogenicity. We immunise mice with virus-like particles (VLPs) containing HIV-1 Gag and the vesicular stomatitis virus envelope glycoprotein G (VSV-G). cGAMP loading of VLPs augments CD4 and CD8 T-cell responses. It also increases VLP- and VSV-G-specific antibody titres in a STING-dependent manner and enhances virus neutralisation, accompanied by increased numbers of T follicular helper cells. Vaccination with cGAMP-loaded VLPs containing haemagglutinin induces high titres of influenza A virus neutralising antibodies and confers protection upon virus challenge. This requires cGAMP inclusion within VLPs and is achieved at markedly reduced cGAMP doses. Similarly, cGAMP loading of VLPs containing the SARS-CoV-2 Spike protein enhances Spike-specific antibody titres. cGAMP-loaded VLPs are thus an attractive platform for vaccination

Distinguishing post-treatment changes from recurrent disease in cholangiocarcinoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Three-dimensional techniques for radiotherapy have expanded possibilities for partial volume liver radiotherapy. Characteristic, transient radiographic changes can occur in the absence of clinical radiation-induced liver disease after hepatic radiotherapy and must be distinguished from local recurrence.</p> <p>Case presentation</p> <p>In this report, we describe computed tomography changes after chemoradiotherapy for cholangiocarcinoma as an example of collaboration to determine the clinical significance of the radiographic finding.</p> <p>Conclusion</p> <p>Because of improved three-dimensional, conformal radiotherapy techniques, consultation across disciplines may be necessary to interpret post-treatment imaging findings.</p

Success of Preoperative Radiotherapy in Inflammatory Breast Cancer with Inadequate Response to Taxane-Based Chemotherapies

Inflammatory breast cancer is a locally-aggressive and highly malignant cancer which often carries a poor prognosis for afflicted patients. Multi-modality treatment is often required, and taxane-based chemotherapy has shown improved outcomes and allowed for the pursuit of mastectomies, which are critical to disease control. Inadequate response to taxane-based chemotherapy indicates aggressive disease, and the role of preoperative radiotherapy for treatment in this patient group and its effects on patient outcomes and toxicity has not been studied. This study evaluates the effectiveness of preoperative radiotherapy on this patient group. Inflammatory breast cancer patients between 2012-2018 who were not deemed appropriate for resection following taxane-based chemotherapy leading to their referral for preoperative radiotherapy were identified. Patient, disease, and pre-surgical treatment characteristics were collected. A statistical analysis of surgical outcomes with regards to conversion to resectability, surgical margins, treatment response, complication rates, and locoregional recurrence was performed. 9 patients received neoadjuvant radiation following their inadequate response to taxane-based chemotherapy. 8 of 9 patients converted to resectable disease, 100% of which achieved R0 mastectomy. Median residual primary disease was 1cm, with a grade 1 toxicity being noted in 1 patient which resolved with conservative management. A single low cervical recurrence was observed 4 years after mastectomy. Based on the results of this study, preoperative radiation should be considered in inflammatory breast cancer patients who do not demonstrate adequate response to taxane-based chemotherapy. Use of preoperative radiotherapy in this patient group may lead to the improvement of patient outcomes and a decrease in treatment toxicity