Claire Y. Fung

Lymphoma of the ocular adnexa: A study of 353 cases.

We studied the cases of 353 patients with lymphoma involving the ocular adnexa diagnosed at the Massachusetts General Hospital between 1974 and 2005. The patients included 153 males and 200 females, aged 7 to 95 years, with a mean age of 64 years. In 277 cases, there was no known history of lymphoma. Seventy-six patients had a history of lymphoma, with the ocular adnexa being involved at relapse or with progression of the previously diagnosed lymphoma. The patients had marginal zone lymphoma (182 cases), follicular lymphoma (80 cases), mantle cell lymphoma (18 cases), small lymphocytic lymphoma/chronic lymphocytic leukemia (13 cases), lymphoplasmacytic lymphoma (4 cases), splenic marginal zone lymphoma (2 cases), low-grade B cell, not subclassified (19 cases), precursor B lymphoblastic lymphoma (3 cases), diffuse large B-cell lymphoma (26 cases), and 1 case each of high-grade B-cell lymphoma, not subclassified, peripheral T-cell lymphoma, unspecified type, extranodal NK/T-cell lymphoma, nasal type, and Hodgkin lymphoma, nodular sclerosis type. Almost all marginal zone lymphoma patients (168 of 182, 92%) had primary ocular adnexal lymphoma. Fourteen marginal zone lymphoma patients (8%) had a prior history of lymphoma, usually arising in another extranodal site. Twenty-five of 80 (31%) follicular lymphoma patients had a prior history of lymphoma, usually arising in lymph nodes. Patients with mantle cell lymphoma, chronic lymphocytic leukemia, lymphoplasmacytic lymphoma, and splenic marginal zone lymphoma almost always had a prior history of lymphoma or were known to have widespread disease at the time of diagnosis of ocular adnexal lymphoma. A subset of the diffuse large B-cell lymphomas were associated with large destructive masses involving adjacent structures such as paranasal sinuses, raising the possibility that they may have arisen from one of the adjacent structures and involved the ocular adnexa by direct extension. The relatively high proportion of low-grade lymphoma, not subclassified, highlights the difficulty that may arise in distinguishing different types of low-grade lymphoma, particularly when biopsies are small and artifactually distorted. Ocular adnexal lymphoma is primarily a disease of older adults, with a slight female preponderance. Most lymphomas are low-grade B-cell lymphomas, with marginal zone lymphoma being by far the most common type. Marginal zone lymphoma typically involves the ocular adnexa primarily, whereas other types of low-grade B-cell lymphoma often involve the ocular adnexa secondarily. High-grade B-cell lymphomas only occasionally involve the ocular adnexa, and T-cell lymphoma, NK-cell lymphoma, and Hodgkin lymphoma are only rarely encountered in this site.

Ocular adnexal lymphoma: Clinical behavior of distinct World Health Organization classification subtypes

PURPOSE To evaluate the clinical behavior and treatment outcome of ocular adnexal lymphomas classified by the World Health Organization system, with emphasis on marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). MATERIALS AND METHODS The clinicopathologic materials from 98 consecutive patients treated for ocular adnexal lymphoma were reviewed. Fourteen patients had prior lymphoma and 84 patients had primary disease (75% Stage I, 6% Stage III, and 19% Stage IV). Radiation (photons/electrons) was administered to 102 eyes to a median dose of 30.6 Gy. The mean follow-up was 82 months. RESULTS The most common subtypes among the primary patients were MALT (57%) and follicular (18%) lymphoma. The 5-year actuarial local control rate in 102 irradiated eyes was 98%. Among the low-grade lymphomas, the 5-year local control rate correlated with the radiation dose in the MALT lymphoma subgroup (n = 53): 81% for <30 Gy and 100% for > or =30 Gy (p <0.01). For the non-MALT low-grade lymphomas such as follicular lymphoma (n = 30), the local control rate was 100% regardless of dose. For 39 Stage I MALT lymphoma patients treated with radiation alone, the distant relapse-free survival rate was 75% at 5 years and 45% at 10 years. Distant relapses were generally isolated and successfully salvaged by local therapy. The overall survival for this subgroup was 81% at 10 years, with no deaths from lymphoma. CONCLUSIONS Dose-response data suggest that the optimal radiation dose for MALT lymphoma of the ocular adnexa is 30.6-32.4 Gy in 1.8-Gy fractions and follicular lymphoma is adequately controlled with doses in the mid-20 Gy range. The substantial risk of distant relapse in Stage I ocular adnexal MALT lymphoma underscores the importance of long-term follow-up for this disease and the need for additional comparative studies of MALT lymphoma of different anatomic sites.

Time-dose considerations in the treatment of anal cancer

PURPOSE To analyze the impact of patient and treatment parameters in concurrent chemoradiation treatment for anal carcinoma. METHODS AND MATERIALS Retrospective review of 50 MO anal cancer patients treated from 1984-1994. Most patients received concurrent 5-FU, mitomycin, and radiation. Local control and disease-free/overall survival were determined and analyzed according to patient and treatment parameters. RESULTS With 43 month median follow-up, projected overall survival is 66% at 5 and 8 years. Disease-free survival is 67% at 5 years and 59% at 8 years. Local control is 70% at 5 and 8 years. Doses of > or =54 Gy are associated with improved 5-year survival (84 vs. 47%, p = 0.02), disease-free survival (74 v. 56%, p = 0.09), and local control (77 vs. 61%, p = 0.04). Although local control, disease-free survival, and overall survival were improved in patients whose overall treatment time was <40 days, this was not statistically significant. Outcome in the four patients with pretreatment hemoglobin (Hgb) <10 appeared worse with 3-year overall survival 50 vs. 68% (p = 0.07), disease-free survival 0 vs. 67% (p = 0.11), and local control 0 vs. 74% (p = 0.05). Projected 5-year overall survival, relapse-free survival, and local control in 4 HIV(+) patients is 0, 75, and 75%. Multivariate analysis reveals that dose (p = 0.02) and Hgb (p = 0.05) independently affect local control, dose (p = 0.02) affects disease-free survival, and dose (p = 0.01), Hgb (p = 0.03), T-stage (p = 0.03), and HIV-status (0.07) independently influence overall survival. CONCLUSION Radiation doses of > or =54 Gy are associated with significantly improved survival and local control in anal cancer patients treated with chemoradiation. Overall treatment times of less than 40 days are associated with a trend towards improved outcome, but this is not significant. Pretreatment hemoglobin <10 is associated with worse treatment outcome. Survival of HIV (+) patient is poor, but the majority of such patients in this series died of intercurrent disease with their anal carcinomas controlled by chemoradiation.

Postoperative radiation therapy for high-risk colon carcinoma.

PURPOSE This study examines the experience of patients treated with postoperative radiation therapy after resection of high-risk colon carcinoma in an effort to assess the potential role of this modality in combination with current systemic therapies. PATIENTS AND METHODS From 1976 to 1989, 203 patients received postoperative radiation therapy with and without concurrent fluorouracil (5-FU) chemotherapy following resection of modified Astler-Coller B2, B3, C2, and C3 colon tumors. Of the 203 patients, 30 (15%) were identified as having residual local tumor after subtotal resection, whereas 173 (85%) had no known residual disease. The 173 patients treated with adjuvant radiation therapy were compared with a historical control group of 395 patients undergoing surgery only. RESULTS Three groups of patients who appeared to benefit from postoperative radiation were identified. Improved local control and recurrence-free survival rates were seen for patients with stage B3 and C3 colon carcinoma treated with postoperative radiation therapy compared with a similarly staged group of patients undergoing surgery only. Irradiated patients whose tumors had an associated abscess or fistula formation had improved local control and recurrence-free survival rates compared with a similar group of patients undergoing surgery only. There appears to be a subset of patients with residual local disease after subtotal resection that may be salvaged by high-dose postoperative radiation therapy. CONCLUSION Selected groups of patients with colon carcinoma may benefit from postoperative radiation in addition to current systemic therapies. Integration of 5-FU and levamisole with postoperative radiation therapy should be considered for patients with (1) stage B3 and C3 lesions, (2) tumors associated with abscess or fistula formation, and (3) residual local disease after subtotal resection.

Prognostic factors in invasive bladder carcinoma in a prospective trial of preoperative adjuvant chemotherapy and radiotherapy.

Clinical and pathologic factors were analyzed in 40 patients with localized muscle-invasive bladder carcinoma treated in a prospective bladder-preserving program consisting of transurethral tumor resection, neoadjuvant chemotherapy (methotrexate, cisplatin, and vinblastine [MCV]), and 4,000 cGy radiotherapy with concurrent cisplatin. Patients with biopsy-proven complete response after chemotherapy and 4,000 cGy radiation received full-dose radiotherapy (6,480 cGy) with cisplatin. Cystectomy was recommended to patients with residual disease. Distant metastasis rate was associated with tumor stage and size: 0% in T2 patients, 39% in T3-4 patients (P = .035), 6% for tumors less than 5 cm, and 59% for tumors greater than or equal to 5 cm (P = .002). Risk of bladder tumor recurrence was higher in patients with tumor-associated carcinoma in situ (CIS; 40%) than those without CIS (6%; P = .075). Papillary tumors and solid tumors both had similar treatment outcomes. By multivariate analysis, tumor stage T2 (P = .04) and absence of CIS (P = .03) were significant predictors of complete response; CIS was predictive of local bladder recurrence (P = .07); and tumor size (P = .03), response after chemoradiotherapy (P = .02), and vascular invasion (P = .08) were associated with distant metastasis. Six of eight local bladder tumor recurrences were superficial tumors. The low actuarial distant metastasis rate of T2 patients (0% at 3 years), the 3-year actuarial overall survival rates for T2 (89%) and T3-4 (50%) patients, and the similar treatment outcomes for papillary versus solid tumors are encouraging when compared with published historical controls. These results provide preliminary evidence (median follow-up, 30 months) that the current chemoradiotherapy regimen may have beneficial effects in the treatment of muscle-invasive bladder carcinoma. The true efficacy of neoadjuvant chemotherapy remains to be proven by ongoing randomized trials.

Spermatic Cord Sarcomas: Sonographic and CT Features

Five patients with sarcomas of the spermatic cord were imaged with sonography and/or computed tomography (CT). The former modality is most helpful in demonstrating the extratesticular origin of the mass and evaluating its scrotal extension for local staging. CT is necessary for pelvic staging and searching for distant metastasis. The fat in liposarcomas was easily identified by CT, although it was not echogenic on sonography. Sonography should be the primary imaging modality for scrotal or inguinal masses. If a neoplasm is found, CT should be used for staging, prior to definitive surgical treatment.

An assessment of the current US radiation oncology workforce: methodology and global results of the American Society for Radiation Oncology 2012 Workforce Study.

PURPOSE To determine the characteristics, needs, and concerns of the current radiation oncology workforce, evaluate best practices and opportunities for improving quality and safety, and assess what we can predict about the future workforce. METHODS AND MATERIALS An online survey was distributed to 35,204 respondents from all segments of the radiation oncology workforce, including radiation oncologists, residents, medical dosimetrists, radiation therapists, medical physicists, nurse practitioners, nurses, physician assistants, and practice managers/administrators. The survey was disseminated by the American Society for Radiation Oncology (ASTRO) together with specialty societies representing other workforce segments. An overview of the methods and global results is presented in this paper. RESULTS A total of 6765 completed surveys were received, a response rate of 19%, and the final analysis included 5257 respondents. Three-quarters of the radiation oncologists, residents, and physicists who responded were male, in contrast to the other segments in which two-thirds or more were female. The majority of respondents (58%) indicated they were hospital-based, whereas 40% practiced in a free-standing/satellite clinic and 2% in another setting. Among the practices represented in the survey, 21.5% were academic, 25.2% were hospital, and 53.3% were private. A perceived oversupply of professionals relative to demand was reported by the physicist, dosimetrist, and radiation therapist segments. An undersupply was perceived by physicians assistants, nurse practitioners, and nurses. The supply of radiation oncologists and residents was considered balanced. CONCLUSIONS This survey was unique as it attempted to comprehensively assess the radiation oncology workforce by directly surveying each segment. The results suggest there is potential to improve the diversity of the workforce and optimize the supply of the workforce segments. The survey also provides a benchmark for future studies, as many changes in the healthcare field exert pressure on the workforce.

DISTINCT MATHEMATICAL BEHAVIOR OF APOPTOTIC VERSUS NON-APOPTOTIC TUMOR CELL DEATH

PURPOSE The presence or absence of a p53-dependent apoptosis response has previously been shown to greatly influence radiosensitivity in tumor cells. Here, we examine clonogenic survival curves for two genetically related oncogene transformed cell lines differing in the presence or absence of p53 and apoptosis. Solid tumor radiosensitivity patterns have been previously described for these lines. MATERIALS AND METHODS Oncogene-transformed fibroblasts derived from E1A + Ras transfection of p53-wild-type or p53-null mouse embryonic fibroblasts were plated as single cells and irradiated at increasing radiation doses in single fractions from 1.5 to 11 Gy. Clonogenic cell survival assays were obtained. Survival data are fit to a linear-quadratic relationship: S = e(-alphaD-betaD2). Apoptosis was assessed and quantitated morphologically by staining with the fluorescent nuclear dye DAPI, by TUNEL assay for DNA fragmentation, and by measurement of apoptotic cysteine protease cleavage activity in cytosolic extracts. RESULTS Whereas radiation triggers massive apoptosis in the presence of p53, it produces no measurable DNA fragmentation, apoptotic cysteine protease cleavage activity, or morphological changes of apoptosis in the cells lacking p53. These contrasting mechanisms of death display dramatically different quantitative behavior: log-survival of apoptotic cells is linearly proportional to dose (S = e(-alphaD)), whereas survival of non-apoptotic (p53 null) is linear-quadratic with a significant quadratic contribution. The surviving fraction at 2 Gy (SF-2) for p53-null cells was 70% verses 12% for p53-intact cells. CONCLUSIONS In this system, apoptosis appears to exhibit a dominance of single-event which produces a very high alpha/beta ratio, and no significant shoulder; whereas non-apoptotic death in this system exhibits a comparatively small linear component, a low alpha/beta ratio, and a larger shoulder.