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Biomedical subjects

Jennifer R Bellon

Publications and source records attributed to Jennifer R Bellon.

12 recordsLinked to original sources
PubMed2006

A prospective study of conservative surgery without radiation therapy in select patients with Stage I breast cancer.

PURPOSE: The effectiveness of radiation therapy (RT) in reducing local recurrence after breast-conserving surgery (BCS) in unselected patients with early stage invasive breast cancer has been demonstrated in multiple randomized trials. Whether a subset of women can achieve local control without RT is unknown. In 1986, we initiated a prospective one-arm trial of BCS alone for highly selected breast-cancer patients. This report updates those results. METHODS AND MATERIALS: Eighty-seven (of 90 planned) patients enrolled from 1986 until closure in 1992, when a predefined stopping boundary was crossed. Patients were required to have a unicentric, T1, pathologic node-negative invasive ductal, mucinous, or tubular carcinoma without an extensive intraductal component or lymphatic-vessel invasion. Surgery included local excision with margins of at least 1 cm or a negative re-excision. No RT or systemic therapy was given. RESULTS: Results are available on 81 patients (median follow-up, 86 months). Nineteen patients (23%) had local recurrence (LR) as a first site of failure (average annual LR: 3.5 per 100 patient-years of follow-up). Other sites of first failure included 1 ipsilateral axilla, 2 contralateral breast cancers, and 4 distant metastases. Six patients developed other (nonbreast) malignancies. Nine patients have died, 4 of metastatic breast cancer and 5 of unrelated causes. CONCLUSIONS: Even in this highly selected cohort, a substantial risk of local recurrence occurred after BCS alone with margins of 1.0 cm or more. These results suggest that with the possible exception of elderly women with comorbid conditions, radiation therapy after BCS remains standard treatment.

Adenocarcinoma, Mucinous↗
PubMed2006

Radiation therapy for breast cancer.

Over the past five decades, radiotherapy (RT) has become an integral part in the combined modality management of breast cancer. Although its significant effect on local control has been long demonstrated, only recently has adjuvant RT been shown to have a significant effect on breast cancer mortality and overall survival. This article summarizes the adjuvant role of RT after mastectomy and lumpectomy, as well as the rationale and techniques for partial-breast irradiation.

Breast Neoplasms↗
PubMed2005

Prospective evaluation of concurrent paclitaxel and radiation therapy after adjuvant doxorubicin and cyclophosphamide chemotherapy for Stage II or III breast cancer.

PURPOSE: To evaluate the safety and feasibility of concurrent radiation therapy and paclitaxel-based adjuvant chemotherapy, given either weekly or every 3 weeks, after adjuvant doxorubicin and cyclophosphamide (AC). METHODS AND MATERIALS: After definitive breast surgery and AC chemotherapy, 40 patients with operable Stage II or III breast cancer received protocol-based treatment with concurrent paclitaxel and radiation therapy. Paclitaxel was evaluated on 2 schedules, with treatment given either weeklyx12 weeks (60 mg/m2), or every 3 weeksx4 cycles (135-175 mg/m2). Radiation fields and schedules were determined by the patient's surgery and pathology. The tolerability of concurrent therapy was evaluated in cohorts of 8 patients as a phase I study. RESULTS: Weekly paclitaxel treatment at 60 mg/m2 per week with concurrent radiation led to dose-limiting toxicity in 4 of 16 patients (25%), including 3 who developed pneumonitis (either Grade 2 [1 patient] or Grade 3 [2 patients]) requiring steroids. Efforts to eliminate this toxicity in combination with weekly paclitaxel through treatment scheduling and CT-based radiotherapy simulation were not successful. By contrast, dose-limiting toxicity was not encountered among patients receiving concurrent radiation with paclitaxel given every 3 weeks at 135-175 mg/m2. However, Grade 2 radiation pneumonitis not requiring steroid therapy was seen in 2 of 24 patients (8%) treated in such a fashion. Excessive radiation dermatitis was not observed with either paclitaxel schedule. CONCLUSIONS: Concurrent treatment with weekly paclitaxel and radiation therapy is not feasible after adjuvant AC chemotherapy for early-stage breast cancer. Concurrent treatment using a less frequent paclitaxel dosing schedule may be possible, but caution is warranted in light of the apparent possibility of pulmonary injury.

Adult↗
PubMed2005

What extent of radiation therapy is standard?

This review will address: (1) 'what are the current indications for radiation therapy (RT), following both mastectomy and breast-conserving surgery?' and (2) 'if RT is indicated, what are the appropriate volumes or 'targets' to be treated?' Given the complexity of these questions, this review will focus on selected topics considered of greatest current interest. In addition, this review will primarily focus on results obtained from randomized clinical trials (RCTs). Finally, we acknowledge an American point of view in our discussion.

Breast Neoplasms↗
PubMed2005

Sequencing of chemotherapy and radiation therapy in early-stage breast cancer: updated results of a prospective randomized trial.

PURPOSE: The optimal integration of chemotherapy with radiation (RT) for patients with early-stage breast cancer remains uncertain. We present the long-term results of a prospective randomized trial to address this question. PATIENTS AND METHODS: Two hundred forty-four patients were randomly assigned after conservative breast surgery to receive 12 weeks of cyclophosphamide, doxorubicin, methotrexate, fluorouracil, and prednisone (CAMFP) before RT (CT-first) or after RT (RT-first). Median follow-up for surviving patients was 135 months. RESULTS: There were no significant differences between the CT-first and RT-first arms in time to any event, distant metastasis, or death. Sites of first failure were also not significantly different. CONCLUSION: Among breast cancer patients treated with conservative surgery, there is no advantage to giving RT before adjuvant chemotherapy. However, this study does not have enough statistical power to rule out a clinically important survival benefit for either sequence.

Adult↗
PubMed2005

CT computer-optimized high-dose-rate brachytherapy with surface applicator technique for scar boost radiation after breast reconstruction surgery.

PURPOSE: Immediate breast reconstruction has become increasingly prevalent after mastectomy for breast cancer. Postoperative scar boost radiation for the reconstructed breast presents many planning challenges due to the shape, size, and curvature of the scar. High-dose-rate (HDR) surface applicator brachytherapy is a novel and effective method of delivering scar boost radiation. Two cases, one with a saline implant and one with a transverse rectus abdominis musculocutaneous flap reconstruction, illustrate the method and advantages of HDR optimization of surface applicators. METHODS AND MATERIALS: For 2 patients a mold of the breast was made with Aquaplast sheets. A reproducible system was used for arm positioning. Skin fiducials, including tattoos from external beam planning, were matched to fiducials on the mold. HDR catheters were sited on the mold at 1cm intervals, with the central catheter situated along the scar. Topographically, both scars demonstrated extreme curvature in both craniocaudal and mediolateral directions. A CT computer-optimized HDR plan was developed, with the reference dose prescribed at the skin surface. The dosimetry was compared to single-field and matched-field electron plans. RESULTS: This surface applicator technique provided a uniform skin dose of 100% to the entire clinical target volume (CTV) without hot spots in both patients. The patient position and surface applicator setup were consistently reproducible. The patients tolerated the treatment well with minimal skin erythema. In the single-field electron plan, skin dose was decreased to 50% at the periphery of the scar. Matching fields addressed this depth dose decrement, but resulted in large localized hot spots of more than 200% centrally in each field. CONCLUSION: CT computer-optimized HDR surface applicator brachytherapy provided a reproducible homogeneous method of treating highly curved scars on the reconstructed breast. Electron beam treatment would result in longer and more complex treatments yet still provide a less homogeneous dose than this surface applicator technique.

Brachytherapy↗
PubMed2004

CNS metastases in breast cancer.

As systemic therapy of metastatic breast cancer improves, CNS involvement is becoming a more widespread problem. This article summarizes the current knowledge regarding the incidence, clinical presentation, diagnosis, prognosis, and treatment of CNS metastases in patients with breast cancer. When available, studies specific to breast cancer are presented; in studies in which many solid tumors were evaluated together, the proportion of patients with breast cancer is noted. On the basis of data from randomized trials and retrospective series, neurosurgery and stereotactic radiosurgery (SRS) may prolong survival in patients with single brain metastases. The treatment of multiple metastases remains controversial, as does the routine use of whole-brain radiotherapy (WBRT) after either surgery or SRS. Although it is widely assumed that chemotherapy is of limited benefit, data from case series and case reports suggest otherwise. WBRT, neurosurgery, SRS, and medical therapy each have a role in the treatment of CNS metastases; however, neurologic symptoms frequently are not fully reversible, even with appropriate therapy. Studies specifically targeted toward this group of patients are needed.

Brain Neoplasms↗
PubMed2004

A prospective study of concurrent cyclophosphamide/methotrexate/5-fluorouracil and reduced-dose radiotherapy in patients with early-stage breast carcinoma.

BACKGROUND: Concurrent administration of chemotherapy and radiotherapy has the potential advantage of delaying neither treatment and providing radiation sensitization. However, the optimal approach to concurrent treatment in women with early-stage breast carcinoma remains undefined. We present updated results of a prospective protocol of concurrent cyclophosphamide/methotrexate/5-fluorouracil (CMF) and reduced-dose radiotherapy, focusing on tumor control and patient tolerance. METHODS: One hundred twelve women with AJCC Stage I or Stage II breast carcinoma with 0-3 positive axillary lymph nodes were enrolled in a prospective single-arm study of concurrent CMF and reduced-dose radiotherapy (39.6 gray [Gy] to the whole breast, 16-Gy boost). A high proportion of women had risk factors associated with an increased risk of local disease recurrence, including age <40 (32%), close or positive margins (37%), or lymphatic/vascular invasion (51%). The median follow-up period was 94 months. RESULTS: The 5-year overall survival rate was 94%. By 60 months, 5 patients (4%) experienced local disease recurrence and 19 patients (17%) experienced distant metastasis. There were no isolated regional lymph node recurrences. Local disease recurrence occurred in 1 of 25 patients (4%), 1 of 16 patients (6%), and 3 of 70 patients (4%) with positive, close (<1 mm), and negative margins, respectively. One patient developed acute myelogenous leukemia. An additional patient developed Grade 2 pneumonitis. Cosmetic results were not recorded uniformly for all patients and therefore could not be reliably analyzed. CONCLUSIONS: Concurrent CMF and reduced-dose radiotherapy resulted in a low level of late toxicity and excellent local tumor control, despite the large proportion of patients with substantial risk factors for local disease recurrence. Future studies of concurrent regimens, particularly in patients at high risk of local disease recurrence, are warranted.

Adult↗
PubMed2004

Evaluation of the internal mammary lymph nodes by FDG-PET in locally advanced breast cancer (LABC).

The presence of internal mammary (IM) lymph node metastases in breast cancer predicts outcome and may alter treatment. Standard imaging has limited usefulness for evaluation of the IM chain because of low sensitivity. Our preliminary studies suggested that [F-18]-2-fluoro-d-glucose positron emission tomography (FDG-PET) improves the detection of IM and mediastinal metastases. We therefore performed a retrospective review of women who underwent FDG-PET prior to treatment to determine the benefit of PET for imaging IM disease. The records of 28 consecutive patients undergoing FDG-PET prior to neoadjuvant chemotherapy for suspected locally advanced breast cancer (LABC) were reviewed. The presence of abnormal IM uptake on FDG-PET was noted. IM uptake on FDG PET was compared with standard radiographic imaging and was correlated with putative risk factors for IM involvement and with clinical patterns of failure. Patients did not undergo IM biopsy; however, patterns of failure were assessed to validate the FDG-PET findings. Clearly abnormal FDG uptake in the IM nodes was seen in 7 of 28 women (25%). Prospective conventional chest imaging failed to identify IM metastases in any patient. IM uptake on PET was associated with large size of the primary tumor (P = 0.03) and with inflammatory disease (P = 0.04). The presence of IM FDG uptake predicted failure by a pattern consistent with spread from IM lymph node metastasis. FDG-PET appears to be a useful noninvasive modality to detect IM metastases in LABC. Pathologic verification in a prospective study is necessary to confirm these findings.

Adult↗
PubMed2003

Human wild-type SEDL protein functionally complements yeast Trs20p but some naturally occurring SEDL mutants do not.

X-linked spondyloepiphyseal dysplasia tarda (SEDT, or SEDL) is a primary skeletal dysplasia affecting mostly spinal vertebral bodies and epiphyses. Previously, we have identified the SEDL gene and determined the spectrum of 21 different SEDL causing mutations. The SEDL gene is a highly conserved gene with an as yet unknown function. The yeast SEDL protein ortholog, Trs20p, has been isolated as a member of a large multi-protein complex ( approximately 10 proteins) called transport protein particle (TRAPP), which is involved in endoplasmic reticulum (ER)-to-Golgi transport. While the SEDL gene mutations cause a tissue-specific (epiphyses) and relatively mild phenotype, the Trs20p function is essential for the yeast cell. We now provide evidence that recombinant human SEDL protein is able to functionally complement the Saccharomyces cerevisiae TRS20 (TRAPP subunit 20 gene) knockout mutant. This finding strongly supports the speculated conserved nature of the SEDL/Trs20p function. To shed further light on the SEDL/Trs20p protein function, five different naturally occurring SEDL gene mutations have been tested in complementation studies. While two truncation mutations (157delAT and C271T) and one missense mutation (G139T) were unable to rescue the trs20Delta lethal phenotype, two other missense mutations (C218T and T389A) did complement trs20Delta. Interestingly, there is no obvious correlation between the nature and position of the SEDL mutation and the clinical severity of the disorder among the human SEDL patients. Although the identification of complementing SEDL gene mutations may suggest the existence of subtle phenotypic differences among SEDL patients, it might also point towards the identification of SEDL protein residues/domains specific for normal, vertebrate bone growth.

Amino Acid Sequence↗
PubMed2002

Evidence for multiple interspecific hybridization in Saccharomyces sensu stricto species.

Fluorescent amplified fragment length polymorphism analysis demonstrates a high level of gene exchange between Saccharomyces sensu stricto species, with some strains having undergone multiple interspecific hybridization events with subsequent changes in genome complexity. Two lager strains were shown to be hybrids between Saccharomyces cerevisiae and the alloploid species Saccharomyces pastorianus. The genome structure of CBS 380(T), the type strain of Saccharomyces bayanus, is also consistent with S. pastorianus gene transfer. The results indicate that the cider yeast, CID1, possesses nuclear DNA from three separate species. Mating experiments show that there are no barriers to interspecific conjugation of haploid cells. Furthermore, the allopolyploid strains were able to undergo further hybridizations with other Saccharomyces sensu stricto yeasts. These results demonstrate that introgression between the Saccharomyces sensu stricto species is likely.

Beer↗