A prospective phase I comparison of toxicity and cosmesis outcomes of single-fraction IORT and hypofractionated radiotherapy with IORT boost in early-stage breast cancer.

PURPOSE: Radiation therapy is proven to reduce local recurrence in patients with early-stage breast cancer. To reduce toxicity, treatment time, and improve accuracy, intraoperative radiation therapy was used as definitive treatment or as a boost. The study's objective was to compare the short-term toxicity and cosmesis of single-fraction (SF) IORT and hypofractionated radiotherapy with IORT boost (HfB) given as definitive treatment. METHODS AND MATERIALS: Between March 2011 and December 2013, 57 patients aged 45-91 years and 24 patients aged 43-83 years (total n = 81) with Stage 0-II were treated with SF or HfB (Mobetron, IntraOp Medical, Sunnyvale, CA). For SF treatment, 21 Gy was delivered using 4.5-6 cm applicators with electron energies from 6 to 12 MeV. For HfB, an intraoperative boost of 10 Gy was delivered using 4-7 cm applicators with energies from 4 to 12 MeV followed by whole-breast radiation with 40.5 Gy over 15 fractions. Toxicity was assessed at 2 weeks, 6 months, and 12 months per Radiation Therapy Oncology Group acute skin toxicity criteria and cosmesis. RESULTS: At 12 months, SF and HfB were well tolerated by all patients with no Grade 3+ toxicity. At 1 year, Grade-2 toxicity was resolved. Ninety-eight percent of SF patients and ninety percent of HfB patients had 0-1 grade toxicity. In the SF and HfB groups, 100% of patients had excellent or good cosmesis at 12-month followup interval. The SF exhibited a more favorable cosmesis with a higher percentage of excellent scores compared with HfB (80.4% vs. 45%; p = 0.0033). CONCLUSIONS: After breast conservation surgery, SF or HfB may be an option for patients with early-stage breast cancer compared to conventional external beam radiotherapy.

Intraoperative radiotherapy for breast cancer: its perceived simplicity.

Over one-quarter of a million cases of breast cancer are diagnosed in the United States each year, many of which are early stage.The radiotherapeutic options after breast-conserving surgery in early-stage breast cancer are evolving quickly, with a focus on minimizing treatment volume, toxicity, and treatment duration. One such emerging option is intraoperative radiotherapy (IORT), administered either as a single fraction or as a boost.With many centers seeking to adopt such technology, there are licensing, proctoring, staffing, technical support, and reimbursement issues that need to be considered. We have reviewed the current international experience and describe one community cancer center's experience with initiating an IORT breast cancer program.

Intraoperative electron radiotherapy boost as a component of adjuvant radiation for breast cancer in the community setting.

To reduce toxicity/treatment time and improve accuracy, intraoperative electron radiotherapy (IOERT) was used as an alternative to electron beam radiation therapy boost. Primary objective was to determine feasibility and acute toxicity. From August 2009 to June 2011, 50 patients (age 32 to 76 years) with in situ or invasive breast cancer (Stage 0 to IIIA) were treated. Toxicity assessed according to standard National Cancer Institute scales. Median tumor size was 20 mm (range, 6 to 80 mm) with 43 infiltrating ductal, two infiltrating lobular, and five ductal in situ carcinoma. A single 10-Gy fraction boost was given to the tumor bed after resection followed by whole-breast radiotherapy. After IOERT, three patients required completion axillary lymph node dissection, eight had reexcision resulting from positive margins, and four opted for completion mastectomy. The median follow-up was 10 months (range, 2 to 24 months). Ten patients had Grade 1 and one reported Grade 2 breast pain 2 weeks after IOERT; all resolved at 6 weeks. Two patients had delay in wound healing, but none developed a wound infection. Three patients reported symptomatic fat necrosis. No other toxicities were reported. IOERT resulted in a reduction in treatment time, was not associated with additional toxicity or change in the acute toxicity profile, and is a feasible treatment option in a community hospital setting.

Motexafin gadolinium: a novel radiosensitizer for brain tumors.

For a variety of reasons, the management of brain tumors, both primary and metastatic, remains a considerable challenge. As most systemic therapies do not cross the BBB at therapeutic doses, radiation and surgery have played primary roles in the management of these diseases. Despite significant advances in surgical techniques and radiation delivery, outcomes for most adult brain tumors continue to be poor. In an effort to enhance the effects of radiation in the brain, a variety of radiation sensitizers, including motexafin gadolinium, have been investigated. In the following manuscript, we summarize motexafin gadolinium and its role in brain tumors.

Motexafin gadolinium: a novel radiosensitizer for brain tumors.

Despite advances in the field of oncology, progress for patients with brain metastases and most primary brain tumors has been slow. New efforts to enhance the therapeutic index of radiation therapy are under way, including the use of radiosensitizers. Motexafin gadolinium (Xcytrin) is one such novel agent with several unique properties that enhance the cytotoxic potential of radiation therapy, as well as several chemotherapeutic agents, and possibly has independent cytotoxicity in certain lymphoid malignancies. Motexafin gadolinium is very well tolerated with tumor specific uptake. The rationale for the use of this drug as well as its current and future role as a radiation enhancer in the management of brain tumors is reviewed.

Non-Hodgkin's lymphoma presenting as a pelvic mass with elevated CA-125.

BACKGROUND: We report a case of pelvic lymphoma with an elevated serum CA-125 level, initially misdiagnosed as ovarian carcinoma. A review of the literature is presented and a possible mechanism for CA-125 elevation in diseases other than ovarian cancer is discussed. CASE: A 50-year-old woman presented with symptoms of progressive dyspnea, early satiety, fatigue, and weight loss. Workup revealed a pelvic mass and an elevated CA-125 level. Paclitaxel and carboplatin were administered to facilitate therapy and provide symptomatic relief for a presumed bulky ovarian carcinoma. A biopsy was obtained after the initiation of chemotherapy, yielding the diagnosis of diffuse large B cell non-Hodgkin's lymphoma, stage II-B. A regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone followed by radiotherapy resulted in long-term disease remission. A search of the literature revealed several clinical series describing the elevation of CA-125 in a variety of diseases, both benign and malignant. CONCLUSIONS: In the setting of a newly diagnosed pelvic mass, care should be taken when interpreting an elevated CA-125 level. While ovarian cancer is high on the list of differential diagnoses, lymphoma cannot be excluded until a tissue diagnosis is obtained.

A phase I study of Topotecan, as a radiosensitizer, for thoracic malignancies.

PURPOSE: To determine the maximum-tolerated dose (MTD) of daily Topotecan with full-dose thoracic radiotherapy (XRT). METHODS AND MATERIALS: Patients with advanced thoracic malignancies requiring full dose radiation received daily I.V. Topotecan prior to each daily session of XRT to 60 Gy over 6 weeks. Dose levels (and subjects studied at each) have been 0.2 (N=7), 0.3 (N=5), 0.4 (N=7), and 0.5mg/m(2) per day (N=5) in a best-of-five design. Tumor response was assessed at 4-8 weeks after completion of therapy. RESULTS: From March 1995 to December 1999, a total of 24 patients were treated. The MTD of Topotecan was 0.4 mg/m(2) per day, based on dose limiting toxicities (DLTs) observed at 0.5 mg/m(2) per day, which were grade 4 hematological toxicities or diarrhea and grade 3 esophagitis. Tumor responses included: zero complete response (CR), nine partial responses (PR), five stable disease (SD), nine progressive disease (PD) and one not evaluated (NE). Additionally, local response was also assessed separately (within the XRT ports) and there were 10 PR, 12 SD, 1 PD, and 1 NE. CONCLUSION: the MTD of Topotecan with concomitant thoracic radiotherapy is 0.4 mg/m(2) per day. The DLTs observed were grade 4 diarrhea, grade 3 esophagitis and grade 4 hematological toxicities. Based on the known radiosensitizing effect of Topotecan, this dose is recommended for phase II testing.