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Objective. Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) is a rare disease with a poor prognosis. SCCOHT has recently been shown to be associated with SMARCA4 gene mutations as well as molecular and genetic similarities to malignant rhabdoid tumors (MRT). The objective of our study is to describe the clinical characteristics, treatment modalities and outcomes of 47 patients with SCCOHT. Methods. We performed a retrospective analysis of 47 patients with SCCOHT evaluated at MD Anderson Cancer Center between 1990 and 2014. Medical records were reviewed for demographic information, pathologic findings, treatment regimens and outcomes. Results. Median age at diagnosis was 30 years (range 5-46). All patients underwent surgery with unilateral salpingo-oophorectomy (USO) performed in 26 patients (55%), and hysterectomy with bilateral salpingooophorectomy (BSO) in 21 patients (45%). Sixteen patients (34.0%) had stage I disease, six (12.8%) stage II, 23 (48.9%) stage III, and two patients (4.3%) had stage IV disease. Information on adjuvant treatment was available for 43 patients: 83.3% received chemotherapy alone, 9.5% chemotherapy followed by radiotherapy, 2.4% chemoradiation, and 4.8% did not receive any adjuvant therapy. Median follow-upwas 13.2 months (range, 0.1 to 210.7) with a median overall survival of 14.9 months. Multi-agent chemotherapy and radiotherapy were associated with a better prognosis. Conclusion. Our findings suggest that aggressive therapy including multi-agent chemotherapy and possibly radiotherapy may extend survival. Further study is needed to improve outcomes in these patients including the adoption of systemic therapies used in MRT as well as the development of novel agents targeting specific mutations. [ABSTRACT FROM AUTHOR]

Purpose: Patients receiving pelvic radiation for cervical cancer experience high rates of acute gastrointestinal (GI) toxicity. The association of changes in the gut microbiome with bowel toxicity from radiation is not well characterized., Methods and Materials: Thirty-five patients undergoing definitive chemoradiation therapy (CRT) underwent longitudinal sampling (baseline and weeks 1, 3, and 5) of the gut microbiome and prospective assessment of patient-reported GI toxicity. DNA was isolated from stool obtained at rectal examination and analyzed with 16S rRNA sequencing. GI toxicity was assessed with the Expanded Prostate Cancer Index Composite instrument to evaluate frequency, urgency, and discomfort associated with bowel function. Shannon diversity index was used to characterize alpha (within sample) diversity. Weighted UniFrac principle coordinates analysis was used to compare beta (between sample) diversity between samples using permutational multivariate analysis of variance. Linear discriminant analysis effect size highlighted microbial features that best distinguish categorized patient samples., Results: Gut microbiome diversity continuously decreased over the course of CRT, with the largest decrease at week 5. Expanded Prostate Cancer Index Composite bowel function scores also declined over the course of treatment, reflecting increased symptom burden. At all individual time points, higher diversity of the gut microbiome was linearly correlated with better patient-reported GI function, but baseline diversity was not predictive of eventual outcome. Patients with high toxicity demonstrated different compositional changes during CRT in addition to compositional differences in Clostridia species., Conclusions: Over time, increased radiation toxicity is associated with decreased gut microbiome diversity. Baseline diversity is not predictive of end-of-treatment bowel toxicity, but composition may identify patients at risk for developing high toxicity., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: Radiation therapy has direct cytotoxic effects on tumor-infiltrating lymphocytes, but it also has immune stimulatory effects that increase immune cell infiltration. The dynamics of these competing effects on immune cells at the site of the tumor are poorly characterized during chemoradiation treatment (CRT) because of the difficulty of obtaining consecutive tumor biopsies. We used a minimally invasive cervical cytobrushing method to analyze the kinetics of intratumoral immune cell changes in patients with cervical cancer during CRT., Methods and Materials: Cervical brushings were obtained from 20 patients with cervical cancer at baseline and during fractionated radiation therapy and cisplatin (weeks 1, 3, and 5). Matching peripheral blood mononuclear cells were obtained from 9 patients at the same time points. Cells were analyzed using multispectral flow cytometry to identify T cell and myeloid cell subsets and their activation status. Changes in immune cell subsets throughout treatment were calculated using matched-pair analysis with Wilcoxon rank sum test., Results: We observed a significant decline in CD3+ total T cells, as well as CD8+ and CD4+ T-cell subsets in the first week of treatment from baseline, followed by variable expansion at weeks 3 and 5. This coincided with higher levels of proliferating CD8+ T cells expressing Ki67 at week 3 of treatment. The percentages of activated CD8+ T cells expressing CD69 continuously increased over the course of treatment, whereas the percentage of activated CD11c+CD11b- dendritic cells was highest during the first week. Many of these changes were not observed in the blood., Conclusions: Our results identified immune dynamic changes during CRT, indicating that CRT may be immune activating at the site of the tumor. This study also suggests the importance of sequential analyses of the local tumor microenvironment in addition to peripheral blood., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to develop a radiation therapy (RT) contouring atlas and recommendations for women with postoperative and locally advanced vulvar carcinoma., Methods and Materials: An international committee of 35 expert gynecologic radiation oncologists completed a survey of the treatment of vulvar carcinoma. An initial set of recommendations for contouring was discussed and generated by consensus. Two cases, 1 locally advanced and 1 postoperative, were contoured by 14 physicians. Contours were compared and analyzed using an expectation-maximization algorithm for simultaneous truth and performance level estimation (STAPLE), and a 95% confidence interval contour was developed. The level of agreement among contours was assessed using a kappa statistic. STAPLE contours underwent full committee editing to generate the final atlas consensus contours., Results: Analysis of the 14 contours showed substantial agreement, with kappa statistics of 0.69 and 0.64 for cases 1 and 2, respectively. There was high specificity for both cases (≥99%) and only moderate sensitivity of 71.3% and 64.9% for cases 1 and 2, respectively. Expert review and discussion generated consensus recommendations for contouring target volumes and treatment for postoperative and locally advanced vulvar cancer., Conclusions: These consensus recommendations for contouring and treatment of vulvar cancer identified areas of complexity and controversy. Given the lack of clinical research evidence in vulvar cancer radiation therapy, the committee advocates a conservative and consistent approach using standardized recommendations., Competing Interests: All other authors report no conflicts of interest., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Primary urethral carcinoma (PUC) is a rare malignancy accounting for <1% of genitourinary cancers, with a predilection for men and African-Americans. The sites and histology of urethral carcinoma vary by gender and anatomical location. Squamous cell carcinoma is most common among both genders but adenocarcinomas are noted in 15-35% of cases among women. Obstructive or irritative symptoms and haematuria are common modes of presentation. Clinical evaluation includes cystourethroscopy with biopsy and examination under anaesthesia. Magnetic resonance imaging provides a highly effective method to image the primary tumour while defıning the potential involvement of surrounding structures. Most tumours are localised, with regional metastases to nodal sites seen in up to 30% of cases in both genders, while distant metastases at presentation are rare (0-6%), but occur in up to 40% of cases with recurrent disease. Among men, the two most important prognostic factors are disease location and stage. Low-stage tumours (T1-2) and tumours involving the fossa navicularis or the penile urethra have a better prognosis than higher stage tumours (>T2 or N+) and lesions involving the bulbomembranous urethra. In women, in addition to stage and location, the size of the tumour has also prognostic implications. While surgery and radiation therapy (RT) are of benefit in early stage disease, advanced stage PUC requires multimodal treatment strategies to optimise local control and survival. These include induction chemotherapy followed by surgery or RT and concurrent chemoradiation with or without surgery. The latter strategy has been used successfully to treat other human papillomavirus-related cancers of the vagina, cervix and anus and may be of value in achieving organ preservation. Given the rarity of PUC, prospective multi-institutional studies are needed to better define the optimal treatment approach for this disease entity., (© 2014 The Authors. BJU International © 2014 BJU International.)

Purpose: To develop a guideline for quality practice of low-dose-rate (LDR) and pulsed-dose-rate (PDR) brachytherapy for locally advanced cervical cancer., Methods: Members of the American Brachytherapy Society (ABS) with expertise in cervical cancer brachytherapy formulated updated guidelines for LDR and PDR brachytherapy for locally advanced (International Federation of Gynecology and Obstetrics [FIGO] Stages IB2-IVA) cervical cancer based on literature review and clinical experience., Results: The ABS strongly recommends the use of brachytherapy as a component of the definitive treatment of locally advanced cervical carcinoma. Precise applicator placement is necessary to maximize the probability of achieving local control without major side effects. The ABS recommends a cumulative delivered dose of approximately 80-90Gy for definitive treatment. Dosimetry must be performed after each insertion before treatment delivery. The dose delivered to point A should be reported for all intracavitary brachytherapy applications regardless of treatment planning technique. The ABS also recommends adoption of the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology guidelines for contouring, image-based treatment planning and dose reporting. Interstitial brachytherapy may be considered for a small proportion of patients whose disease cannot be adequately encompassed by intracavitary application and should be performed by practitioners with special expertise in these procedures. Quality management measures must be performed, and follow-up information should also be obtained., Conclusions: Updated ABS guidelines are provided for LDR and PDR brachytherapy for locally advanced cervical cancer. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their clinical practices and to adopt dose-reporting policies that are critical for outcome analysis., (Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To develop recommendations for the use of adjuvant vaginal cuff brachytherapy after hysterectomy and update previous American Brachytherapy Society (ABS) guidelines., Methods and Materials: A panel of members of the ABS performed a literature review, supplemented their clinical experience, and formulated recommendations for adjuvant vaginal cuff brachytherapy., Results: The ABS endorses the National Comprehensive Cancer Network guidelines for indications for radiation therapy for patients with endometrial cancer and cervical cancer and the guidelines on quality assurance of the American Association on Physicists in Medicine. The ABS made specific recommendations for applicator selection, insertion techniques, target volume definition, dose fractionation, and specifications for postoperative adjuvant vaginal cuff therapy. The ABS recommends that applicator selection should be based on patient anatomy, target volume geometry, and physician judgment. The dose prescription point should be clearly specified. Suggested doses were tabulated for treatment with brachytherapy alone, and in combination with external beam radiation therapy, when applicable. A properly fitted brachytherapy applicator should be selected that conforms to the vaginal apex and achieves mucosal contact with optimal tumor and normal tissue dosimetry. Dose prescription points may be individually selected but doses should be reported at the vaginal surface and at 0.5-cm depth., Conclusions: Recommendations are made for adjuvant vaginal cuff brachytherapy. Practitioners and cooperative groups are encouraged to use these recommendations to formulate their treatment and dose reporting policies. These recommendations will permit meaningful comparisons of reports from different institutions and lead to better and more appropriate use of vaginal brachytherapy., (Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: In 2004, the American Society for Radiation Oncology (ASTRO) published its first physics education curriculum for residents, which was updated in 2007. A committee composed of physicists and physicians from various residency program teaching institutions was reconvened again to update the curriculum in 2009., Methods and Materials: Members of this committee have associations with ASTRO, the American Association of Physicists in Medicine, the Association of Residents in Radiation Oncology, the American Board of Radiology (ABR), and the American College of Radiology. Members reviewed and updated assigned subjects from the last curriculum. The updated curriculum was carefully reviewed by a representative from the ABR and other physics and clinical experts., Results: The new curriculum resulted in a recommended 56-h course, excluding initial orientation. Learning objectives are provided for each subject area, and a detailed outline of material to be covered is given for each lecture hour. Some recent changes in the curriculum include the addition of Radiation Incidents and Bioterrorism Response Training as a subject and updates that reflect new treatment techniques and modalities in a number of core subjects. The new curriculum was approved by the ASTRO board in April 2010. We anticipate that physicists will use this curriculum for structuring their teaching programs, and subsequently the ABR will adopt this educational program for its written examination. Currently, the American College of Radiology uses the ASTRO curriculum for their training examination topics. In addition to the curriculum, the committee updated suggested references and the glossary., Conclusions: The ASTRO physics education curriculum for radiation oncology residents has been updated. To ensure continued commitment to a current and relevant curriculum, the subject matter will be updated again in 2 years., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Despite the widespread use of intensity-modulated radiation therapy (IMRT) for approximately a decade, a lack of adequate guidelines for documenting these treatments persists. Proper IMRT treatment documentation is necessary for accurate reconstruction of prior treatments when a patient presents with a marginal recurrence. This is especially crucial when the follow-up care is managed at a second treatment facility not involved in the initial IMRT treatment. To address this issue, an American Society for Radiation Oncology (ASTRO) workgroup within the American ASTRO Radiation Physics Committee was formed at the request of the ASTRO Research Council to develop a set of recommendations for documenting IMRT treatments. This document provides a set of comprehensive recommendations for documenting IMRT treatments, as well as image-guidance procedures, with example forms provided.

Introduction: Previous reports have suggested that patients who have undergone pelvic radiation for cervical cancer are at risk for developing poorly differentiated endometrial cancers with poor prognoses., Materials and Methods: We conducted a retrospective chart and histologic review of patients from Memorial Sloan-Kettering Cancer Center and MD Anderson Cancer Center diagnosed with endometrial cancer after radiation therapy (RT) for cervical cancer from 1976 to 2000. The comparison group comprised MSKCC endometrial cancer patients whose tumors were not radiation associated ("sporadic cancers")., Results: We identified 23 patients who developed endometrial carcinoma or carcinomasarcoma after RT for cervical carcinoma and 527 sporadic endometrial cancer patients. When radiation-associated endometrial cancers (RAECs) were compared with sporadic cancers, significant differences were noted with regard to stage, grade and histologic subtype distribution. In the RAEC group, there were 16 (70%) stages III and IV cancers compared with 101 (19%) in the sporadic group (P<0.001). There were 20 (87%) grade 3 cancers in the RAEC group versus 161 (31%) in the sporadic group (P<0.001). There were 16 (70%) high-risk histologic subtypes (serous, clear cell, carcinosarcoma, undifferentiated) in the RAEC group versus 79 (15%) in the sporadic group (P<0.001). Median survival in the RAEC group was 24 months versus not reached in the sporadic group (P<0.001). Radiation remained a significant factor for poor prognosis in a stratified analysis, in which we compared sporadic and RAEC cancers controlled for age, histology, grade and stage. However, radiation lost significance in a multivariate analysis, in which stage- and grade-matched cancers from both groups were compared., Discussion: The clinicopathologic characteristics of RAECs, which include a preponderance of high-stage, high-grade and high-risk histologic subtypes, indicate that these tumors differ from sporadic endometrial carcinomas. However, patients with RAECs do not appear to have a significantly worse prognosis when compared with patients with high-stage and high-grade sporadic cancers.

We performed a Monte Carlo study to compare dose distributions for a Fletcher-Suit-Delclos (FSD) ovoid used with (137)Cs low-dose-rate (LDR) sources with those for a Fletcher-Williamson (FW) ovoid used with an (192)Ir pulsed-dose-rate (PDR) source for intracavitary brachytherapy of cervical cancer. We recently reported on extensive validation of Monte Carlo MCNPX models of these ovoids using radiochromic film measurements. Here, we compared these models assuming identical loading of 10, 15 and 20 mgRaEq (72, 108 and 145 cGy cm(2) h(-1), respectively) in three dose mesh planes: one perpendicular to the ovoid long axis bisecting the ovoid, one parallel to and displaced 2 cm medially from the long axis of the ovoid, and a 'rectal' plane perpendicular to the long axis located 1 cm distal to the distal face of the ovoid cap. The FW ovoid delivered slightly higher doses (within 10%) over all loadings to regions away from the bladder and rectal shields when compared to the FSD ovoid. However, the FW ovoid delivered much higher doses (>50%) in regions near these shields. In the rectal plane, the FW ovoid delivered a slightly higher dose, but within the region directly behind the rectal shield, the FW ovoid delivered a dose ranging from +35% to -35% of the FSD dose distribution. We attribute these differences to intrinsic differences in source characteristics (radial dose function and anisotropy factors) and extrinsic factors such as the solid-angle effect between sources and shields and applicator design.

Purpose/objective: To analyze the details of brachytherapy practice in patients treated for carcinoma of the cervix in the United States between 1996 and 1999., Methods and Materials: Radiation facilities were selected from a stratified random sample. Patients were randomly selected from lists of eligible patients treated at each facility. A total of 442 patients' records were reviewed in 59 facilities to obtain data about patients' characteristics, evaluation, tumor extent, and treatment. National estimates were made using weights that reflected the relative contribution of each institution and of each patient within the sampled institutions. From our survey we estimate that 16,375 patients were treated in the United States during this study period. Unless otherwise specified, brachytherapy practice was based on the 408 patients who had their brachytherapy or all their treatment at the surveyed facility., Results: A total of 91.5% of patients underwent brachytherapy at the initial treating institution; 8.5% were referred to a second site for brachytherapy. Forty-two percent of U.S. facilities referred at least some patients to a second facility for brachytherapy. Of U.S. facilities that treated < or =2 eligible patients per year, 61% referred all of their patients to a second facility for brachytherapy or treated with external RT alone; none of the U.S. facilities with larger experience (>2 eligible patients per year) referred all their patients to a second facility for brachytherapy treatment, but 28% referred some patients to an outside facility for brachytherapy. Overall, 94% of patients who completed treatment with curative intent received brachytherapy. Of these patients who had brachytherapy, 77.8%, 13.3%, and 0.9%, respectively, were treated with low-dose-rate (LDR), high-dose-rate (HDR), or a combination of HDR and LDR brachytherapy; 7.9% had interstitial brachytherapy (5.7% LDR and 1.9% HDR, 0.3% mixed). In facilities that treated >2 patients per year, 15.5% and 9.4% of brachytherapy procedures included HDR or interstitial, respectively; in facilities that treated fewer patients, 3.4% had HDR brachytherapy, and only 1.2% had interstitial brachytherapy. Patients treated with LDR intracavitary radiotherapy had one (23.5%), two (74.1%), or three (2.4%) implants. For patients treated with curative intent who completed radiation therapy with LDR intracavitary radiation therapy without hysterectomy, the median brachytherapy dose to Point A was 40.3 Gy, and the median total dose to Point A was 82.9 Gy. Patients were treated with HDR intracavitary radiation therapy using a variety of treatment schedules using 1-2 fractions (7.5%), 3-4 fractions (17.4%), 5-6 fractions (38.5%), 7-9 fractions (33.5%), or 12 fractions (3%). Fraction sizes were <500 cGy (29.5%), 500-<600 (25.2%), 600 (28.1%), >600 (8%), or unknown (9.2%). For patients treated with HDR, the median total dose to Point A (corrected for fraction size using a alpha/beta = 10) was 85.8 Gy (range: 56.2-116.1 Gy). At institutions treating <500 new patients per year, the percentage of patients receiving a brachytherapy dose <40 Gy was significantly higher than at institutions treating > or =500 new patients per year (p < 0.0001). For LDR intracavitary radiation therapy, 5.8% had neither bladder nor rectal doses recorded for any of their implants, whereas in HDR intracavitary radiation therapy, 73.4% had neither bladder nor rectal doses recorded for any of their implants. The median total duration of radiation therapy was identical for patients who had HDR or LDR intracavitary radiation therapy (57 days). For LDR at institutions treating <500 new patients per year, the percentage of patients with treatment duration >56 days was significantly greater than at institutions > or =500 new patients per year (p = 0.002). Of the patients who had LDR intracavitary radiation therapy implants, 65% were treated using tandem and shielded Fletcher-Suit-Delclos colpostats; other patients had mini ovoids (10.9%), cylinders (3.9%), Henschke (3.7%), or other/mixed applicators (16.5%). In contrast, of patients treated with HDR intracavitary radiation therapy, 68.7% had tandem and rings, 18.2% Fletcher-Suit-Delclos ovoids, 7.5% mini ovoids, 2.3% cylinders, and 3.2% other or mixed applicators., Conclusions: The median duration of treatment and median Point A dose were very similar for patients treated with HDR or LDR. Patients with HDR were treated using a variety of treatment schedules. Different applicator types were favored for LDR vs. HDR. Of patients treated with HDR, 73.4% had no brachytherapy bladder or rectal doses recorded, suggesting that full dosimetric calculations were performed only for the first fraction in many institutions. Facility size significantly impacted on referral to another institution for brachytherapy, brachytherapy dose, and treatment duration.

Purpose: To compare quality of life and sexual functioning in cervical cancer survivors treated with either radical hysterectomy and lymph node dissection or radiotherapy., Methods: Women were interviewed at least 5 years after initial treatment for cervical cancer. Eligible women had squamous cell tumors smaller than 6 cm at diagnosis, were currently disease-free, and had either undergone surgery or radiotherapy, but not both. The two treatment groups were then compared using univariate analysis and multivariate linear regression with a control group of age- and race-matched women with no history of cancer., Results: One hundred fourteen patients (37 surgery, 37 radiotherapy, 40 controls) were included for analysis. When compared with surgery patients and controls using univariate analysis, radiation patients had significantly poorer scores on standardized questionnaires measuring health-related quality of life (physical and mental health), psychosocial distress and sexual functioning. The disparity in sexual function remained significant in a multivariate analysis. Univariate and multivariate analyses did not show significant differences between radical hysterectomy patients and controls on any of the outcome measures., Conclusion: Cervical cancer survivors treated with radiotherapy had worse sexual functioning than did those treated with radical hysterectomy and lymph node dissection. In contrast, these data suggest that cervical cancer survivors treated with surgery alone can expect overall quality of life and sexual function not unlike that of peers without a history of cancer.

Objective: To evaluate patients with vulvar cancer who experienced a recurrence after undergoing lymphatic mapping and sentinel lymph node (SLN) biopsy., Methods: We reviewed the records of 52 patients who underwent vulvectomy and lymphatic mapping with blue dye for treatment of vulvar cancer at our institution from 1993 to 1999 and identified patients who experienced recurrent disease., Results: Fourteen (27%) of 52 patients experienced a recurrence. The patients' median age was 60 years (range 35-84 years). Nine patients had squamous lesions, four patients had melanoma, and one patient had Paget's disease with stromal invasion. Four tumors were stage T1, seven were T2, and three were T3. Eight lesions were located at the midline and six were lateral. Thirteen patients underwent superficial inguinal lymphadenectomy while one patient underwent SLN biopsy only. Postoperatively, seven patients underwent no further treatment, six underwent radiation therapy, and one patient underwent chemotherapy. The median follow-up was 46 months and the median disease-free interval was 21 months. Primary recurrence was in the vulva in eight patients (57%), in the groin in three patients (21%), and distant in three patients (21%). Nine of 32 (22%) squamous lesions recurred, four (57%) of seven melanomas recurred, and the sole patient with invasive Paget's recurred. Patient weight was found to be significantly different between patients who experienced a recurrence and those who did not (P = 0.05). At least one SLN was identified in 46 (88%) of the 52 patients. One (17%) of six patients in whom no SLN was identified experienced a recurrence, and 13 (28%) of 46 patients in whom a SLN was identified experienced a recurrence (P = 0.5). In the 41 patients with negative SLNs and negative non-SLNs, the recurrence rate was 24%; in the six patients with positive SLNs and negative non-SLNs, the recurrence rate was 40%; and in the five patients with positive SLNs and positive non-SLNs, the recurrence rate was 40% (P = 0.6). No patients had a negative SLN and positive non-SLN. Of the three patients who experienced a recurrence in the groin, one had a negative SLN and negative non-SLN, one had a positive SLN and positive non-SLN, and one had no SLN identified and a negative non-SLN., Conclusions: . This heterogeneous group of patients who underwent lymphatic mapping with blue dye had similar patterns of recurrence to reported series of patients who did not undergo lymphatic mapping. Groin relapse following a negative SLN biopsy is of concern and suggests that long-term follow-up data are required before lymphatic mapping and SLN biopsy alone can be considered standard treatment for patients with vulvar cancer.

Purpose: To evaluate the efficacy and toxicity of twice-daily external irradiation to the pelvis with brachytherapy for carcinoma of the cervix in a long-term follow-up study., Methods and Materials: This study was designed to administer twice-daily irradiation doses of 1.2 Gy to the pelvis, 5 d/wk. Radiotherapy also included one or two low-dose-rate intracavitary implants, to deliver a total minimal dose of 85 Gy to point A and 65 Gy to the lateral pelvic lymph nodes., Results: Eighty-one patients with clinical Stage IB-IVA carcinoma of the cervix were enrolled in this prospective, single arm, Phase I/II study. Hyperfractionated irradiation was completed in 88%. Brachytherapy was given in two implants in 46% and in one implant in 54%. Six patients had acute Grade 3 toxicities. The cumulative rate of Grade 3 and 4 late effects for patients with Stage IB2, IIA, and IIB disease was 7% at 3 years, 7% at 5 years, and 10% at 8 years. For patients with Stage III and IVA disease, the rate of late toxicities (Grades 3 and 4) was 7% at 3 years and 12% at 5 years. The site of first failure was in the pelvis in 41%, para-aortic or supraclavicular lymph nodes in 6%, and other distant metastatic sites in 14%. The absolute survival rate was 61% at 3 years, 48% at 5 years, and 45% at 8 years. The disease-free survival rate was 43% at 3 years, 38% at 5 years, and 33% at 8 years., Conclusion: The results suggest that, combined with brachytherapy, hyperfractionated irradiation to total parametrial doses about 10% greater than doses administered with standard fractionation pelvic irradiation was tolerated and at least appears to be as effective as standard fractionation pelvic irradiation.

Objective: Our goal was to provide health-care providers, patients, and the general public with an assessment of currently available data regarding the use of adjuvant therapy for breast cancer., Participants: The participants included a non-Federal, non-advocate, 14-member panel representing the fields of oncology, radiology, surgery, pathology, statistics, public health, and health policy as well as patient representatives. In addition, 30 experts in medical oncology, radiation oncology, biostatistics, epidemiology, surgical oncology, and clinical trials presented data to the panel and to a conference audience of 1000., Evidence: The literature was searched with the use of MEDLINE(TM) for January 1995 through July 2000, and an extensive bibliography of 2230 references was provided to the panel. Experts prepared abstracts for their conference presentations with relevant citations from the literature. Evidence from randomized clinical trials and evidence from prospective studies were given precedence over clinical anecdotal experience., Consensus Process: The panel, answering predefined questions, developed its conclusions based on the evidence presented in open forum and the scientific literature. The panel composed a draft statement, which was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately after its release at the conference and was updated with the panel's final revisions. The statement is available at http://consensus.nih.gov., Conclusions: The panel concludes that decisions regarding adjuvant hormonal therapy should be based on the presence of hormone receptor protein in tumor tissues. Adjuvant hormonal therapy should be offered only to women whose tumors express hormone receptor protein. Because adjuvant polychemotherapy improves survival, it should be recommended to the majority of women with localized breast cancer regardless of lymph node, menopausal, or hormone receptor status. The inclusion of anthracyclines in adjuvant chemotherapy regimens produces a small but statistically significant improvement in survival over non-anthracycline-containing regimens. Available data are currently inconclusive regarding the use of taxanes in adjuvant treatment of lymph node-positive breast cancer. The use of adjuvant dose-intensive chemotherapy regimens in high-risk breast cancer and of taxanes in lymph node-negative breast cancer should be restricted to randomized trials. Ongoing studies evaluating these treatment strategies should be supported to determine if such strategies have a role in adjuvant treatment. Studies to date have included few patients older than 70 years. There is a critical need for trials to evaluate the role of adjuvant chemotherapy in these women. There is evidence that women with a high risk of locoregional tumor recurrence after mastectomy benefit from postoperative radiotherapy. This high-risk group includes women with four or more positive lymph nodes or an advanced primary cancer. Currently, the role of postmastectomy radiotherapy for patients with one to three positive lymph nodes remains uncertain and should be tested in a randomized controlled trial. Individual patients differ in the importance they place on the risks and benefits of adjuvant treatments. Quality of life needs to be evaluated in selected randomized clinical trials to examine the impact of the major acute and long-term side effects of adjuvant treatments, particularly premature menopause, weight gain, mild memory loss, and fatigue. Methods to support shared decision-making between patients and their physicians have been successful in trials; they need to be tailored for diverse populations and should be tested for broader dissemination.

The use of ICRT is a critical component in the successful treatment of cervical carcinoma with radiation therapy. Low dose rate ICRT allows optimization of the therapeutic ratio by utilizing physical and radiobiological principles. An optimal geometric relationship among the intracavitary applicators, the tumor, and other pelvic tissues is critically important in maximizing tumor control rates while simultaneously minimizing normal tissue complication rates. Treatment policies that have judiciously combined EBRT and LDR ICRT have achieved very high tumor control rates while maintaining acceptable complication rates. The use of HDR ICRT forfeits some of the radiobiological advantage of LDR ICRT. It remains to be determined whether this difference will have significant clinical consequences.

Background and Methods: We compared the effect of radiotherapy to a pelvic and para-aortic field with that of pelvic radiation and concurrent chemotherapy with fluorouracil and cisplatin in women with advanced cervical cancer. Between 1990 and 1997, 403 women with advanced cervical cancer confined to the pelvis (stages IIB through IVA or stage IB or IIa with a tumor diameter of at least 5 cm or involvement of pelvic lymph nodes) were randomly assigned to receive either 45 Gy of radiation to the pelvis and para-aortic lymph nodes or 45 Gy of radiation to the pelvis alone plus two cycles of fluorouracil and cisplatin (days 1 through 5 and days 22 through 26 of radiation). Patients were then to receive one or two applications of low-dose-rate intracavitary radiation, with a third cycle of chemotherapy planned for the second intracavitary procedure in the combined-therapy group., Results: Of the 403 eligible patients, 193 in each group could be evaluated. The median duration of follow-up was 43 months. Estimated cumulative rates of survival at five years were 73 percent among patients treated with radiotherapy and chemotherapy and 58 percent among patients treated with radiotherapy alone (P=0.004). Cumulative rates of disease-free survival at five years were 67 percent among patients in the combined-therapy group and 40 percent among patients in the radiotherapy group (P<0.001). The rates of both distant metastases (P<0.001) and locoregional recurrences (P<0.001) were significantly higher among patients treated with radiotherapy alone. The seriousness of side effects was similar in the two groups, with a higher rate of reversible hematologic effects in the combined-therapy group., Conclusions: The addition of chemotherapy with fluorouracil and cisplatin to treatment with external-beam and intracavitary radiation significantly improved survival among women with locally advanced cervical cancer.

Modern intracavitary brachytherapy carefully combined with megavoltage external beam radiotherapy is responsible for the high cure rates achieved with radiation treatment of invasive cervical cancers. Pelvic disease recurrence is rare after treatment of patients with tumors < 5 cm in diameter, and even patients with massive tumors 8-10 cm in diameter are cured in 30-50% of cases. Inoperable adenocarcinomas of the endometrium and superficial cancers of the vagina are also effectively treated with intracavitary irradiation. The relative radioresistance of the uterus and vagina, physical advantages resulting from exploitation of the inverse square law, and the radiobiological advantages of low dose rate radiation have combined to make intracavitary irradiation a critical tool in the management of many gynecologic neoplasms.

We present a child with a rare and chemotherapy-resistant form of soft-tissue cancer, low-grade fibromyxoid sarcoma, first noted when he was 4 years old. He is the youngest patient reported to date. An 11-year-old white male presented to. The University of Texas M.D. Anderson Cancer Center's Department of Pediatrics with a 7-year history of right thigh mass and pulmonary nodules, confirmed on examination. He had undergone extensive prior chemotherapy and surgery. He received chemotherapy with high-dose cyclophosphamide (7 g/m2) and later etoposide (150 mg/m2/day x 5), with only slight shrinkage of the thigh mass and none in the lungs. Subsequently the tumor in his proximal thigh and his lung metastases were resected, and radiation therapy was administered to the thigh. His disease remained stable for 12 months, but he then developed a pleural-based metastasis on the left side and new bilateral lung metastases also. The tumors on the left side were removed; residual disease is stable after treatment for 6 months with subcutaneous alpha-interferon-2b. Low-grade fibromyxoid sarcoma is very uncommon in children. It grows slowly and metastasizes to distant organs, chiefly to the lungs. It is resistant to conventional chemotherapy, and thus far only surgery seems to have a life-prolonging effect. Newer chemotherapeutic and possibly biologic agents should be tried in future patients, in order to find an effective way to control the disease.

Background: Cutaneous T-cell lymphoma (CTCL) may respond to many therapies, but long-term disease-free survival is uncommon. Patients with advanced disease have a median survival of approximately 3 years., Objective: Our purpose was to combine known effective agents sequentially to determine whether we could achieve remission in more patients or for longer duration., Methods: Patients with mycosis fungoides (n = 23) or Sézary syndrome (n = 5) were treated with 4 months of recombinant interferon alfa together with isotretinoin, followed by total skin electron beam therapy alone (for stage I to II disease) or preceded by chemotherapy (for stage III to IV disease). Maintenance therapy consisted of interferon for 1 year and topical nitrogen mustard for 2 years., Results: Twenty-eight patients were treated. The overall response rate (complete and partial remissions) was 82%. Although the median duration of remission was 5 months in patients with stage III to IV disease, two patients remain in complete remission at 39 + and 46 + months. In patients with stage I to II disease the median duration of remission has not been reached at a median follow-up of 18 months. Five patients, all with stage III to IV disease, have died. Overall, the regimen was well tolerated with one treatment-related death from neutropenic sepsis., Conclusion: Combined modality therapy may be effective for the treatment of CTCL with similar response rates to other current therapies.

Investigators disagree about the role of adjuvant hysterectomy after irradiation of bulky stage IB cervical carcinomas, although the benefit of combined treatment has never been clearly demonstrated. Studies that have correlated outcome with initial tumor diameter suggest that central recurrences are rare after irradiation of tumors less than 5 cm in diameter, leaving little room for improvement with additional local treatment. Early studies suggested that adjuvant hysterectomy may improve pelvic disease control for patients with bulky endocervical tumors, but these results may have reflected the selection of tumors with relatively favorable characteristics for combined treatment. Several studies have suggested that central pelvic disease can be controlled in more than 90% of patients with bulky endocervical tumors if they are treated with adequate doses of irradiation. Although published studies are somewhat limited by their retrospective designs, the available data do not support the added cost and morbidity of adjuvant hysterectomy in the routine treatment of patients with bulky early stage cervical carcinomas.

Background: Ureteral stricture is a rare late complication of curative radiotherapy for carcinoma of the cervix. A retrospective study was performed to determine the incidence and latency of radiation-induced ureteral stricture, to investigate possible contributing factors, and to compare the time course and presenting characteristics of ureteral compromise caused by late radiation injury or tumor recurrence., Methods: The records of 1784 patients with FIGO stage IB carcinoma of the cervix treated with radiotherapy at The University of Texas M. D. Anderson Cancer Center between 1960 and 1989 were reviewed. The characteristics of patients who developed ureteral stricture as a first manifestation of recurrent disease or without evidence of pelvic recurrence were compared. The risk of ureteral compromise was calculated actuarially., Results: There were 29 patients with severe radiation-induced ureteral stricture. The overall incidences of severe ureteral stenosis were 1.0, 1.2, 2.2, and 2.5% at 5, 10, 15, and 20 years, respectively, reflecting a continuous actuarial risk increase of approximately 0.15% per year. Four patients died of complications from bilateral ureteral stricture. Patients who were treated with centrally blocked external fields or who received more than two transvaginal radiation treatments were at increased risk for developing ureteral stenosis. The risk was similar for patients treated with radiation alone or followed by extrafascial hysterectomy., Conclusions: During the first 5 years after treatment, tumor recurrence is the most common cause of ureteral stricture in patients treated with radiotherapy for carcinoma of the cervix. However, radiation injury to the ureter, although rare, may not become apparent for many years, necessitating continued vigilance throughout the lives of these patients.

A 27-month-old boy of Hispanic background developed multiple cranial nerve palsies, difficulty swallowing, bloody nasal discharge, and irritability. Radiographic evaluations showed extensive destruction of the clivus by a large tumor that invaded the sphenoid bone, left cavernous sinus, ethmoid sinus, nasal cavity, and left orbit. Multiple pulmonary nodules were also noted. The bone marrow and spinal fluid showed no evident tumor cells. Transnasal biopsy revealed a chordoma. Treatment was initiated with a combination of ifosfamide, mesna, and etoposide along with radiation therapy to the cranial tumor. Shifting pulmonary densities were noted on serial films. Despite some clinical improvement, the child developed rapidly progressive hypoxemia 3 weeks after admission and died. Autopsy showed persistent viable tumor in the primary site and massive pulmonary arteriolar tumor emboli, infarcts, and widespread lung parenchymal metastases. No other sites of tumor involvement were discovered. This is the second child reported with intracranial chordoma, pulmonary metastases at diagnosis, and early death attributed to pulmonary tumor emboli.

Purpose: To define the influence of tumor size and morphology on rates of central tumor control (CTC), pelvic tumor control (PTC), and disease-specific survival (DSS) in patients treated with radiotherapy for squamous cell carcinoma of the intact uterine cervix., Methods and Materials: Records of 1526 patients treated with radiotherapy for FIGO Stage IB squamous cell carcinoma of the intact uterine cervix between 1960 and 1989 were retrospectively reviewed. The maximum tumor or cervical diameter was determined from clinical descriptions for 1494 patients. Tumors were divided into nine size categories. Tumors > or = 4 cm were further classified according to the dominant morphology (i.e., exophytic or endocervical). Median follow-up was 12.2 years. Five-year CTC, PTC, and DSS rates were calculated actuarially., Results: CTC, PTC, and DSS rates correlated strongly with tumor diameter (p < 0.0001). Overall, CTC, PTC, and DSS rates for patients with tumors < 5 cm were 99%, 97%, and 88%, respectively. For patients with tumors 5-7.9 cm these rates were 93%, 84%, and 69%, respectively. There were no significant differences in the rates of PTC, CTC, or DSS between subgroups of patients with lesions 5-7.9 cm in diameter. The rates of CTC (97%) and DSS (76%) for patients with 5-7.9 cm exophytic tumors were significantly better than those for patients with endocervical tumors of the same size (91% and 66%, respectively); there was no difference in the PTC rate., Conclusion: Although the CTC rates were excellent for all patients with tumors < 8 cm in diameter, these rates for tumors < 5 cm (99%) and for exophytic tumors 5-7.9 cm (97%) make it difficult to justify the use of adjuvant hysterectomy. Although patients with tumors of 5-7.9 cm had consistently poorer PTC and DSS rates than did patients with smaller tumors, the control rates achieved with aggressive radiotherapy were still excellent. The strong correlation between tumor size and outcome suggests that tumor diameter should be assessed when tumors are clinically evaluated and staged and when treatment results are reported for patients with FIGO Stage IB carcinoma of the uterine cervix.

Purpose: To evaluate the relationship between brachytherapy dose and outcome in patients treated with external radiotherapy (40 Gy to the whole pelvis) and intracavitary radium therapy for bulky endocervical tumors., Methods and Materials: Between 1962 and 1985, 98 patients with Stage IB-IIB bulky endocervical carcinomas (> or = 6 cm in diameter) treated with radiotherapy alone received 40 Gy to the whole pelvis followed by 2 or more intracavitary treatments. Twenty-five patients received < 6000 mg-hr of intracavitary treatment and 73 received > or = 6000 mg-hr (an average dose to point A of approximately 49 Gy). Brachytherapy exposures ranged from 4800-7885 mg-hrs., Results: Patients who received < 6000 mg-hr tended to have unfavorable (narrow) vaginal anatomy (p < 0.01) and to be treated in the later years of the study (p < 0.01). The high-dose group included a somewhat greater proportion of patients with positive lymphangiograms or poor responses to initial external beam treatment. Despite having somewhat more favorable tumors, patients who received less than 6000 mg-hr had a higher rate of pelvic disease recurrence at 5 years (33%) than those who received higher doses (16%) (p = 0.03). Actuarial survival rates at 5 years were 44% and 60% for the low- and high-dose groups, respectively (p = 0.14). Among those who received more than 6000 mg-hr, there was no significant relationship between brachytherapy dose and pelvic disease control. Calculated actuarially, the rate of major (> or = grade 3) complications at 5 years was 23% in the low-dose group and 10% in the high-dose group (p = 0.1)., Conclusions: The relatively high incidence of pelvic disease recurrence and complications in patients who receive less than 6000 mg-hr reflects the narrow therapeutic window for complication-free pelvic disease control in patients with bulky central disease and unfavorable normal tissue anatomy. The results also demonstrate a high pelvic control rate and acceptable morbidity in patients with favorable anatomy treated with high-dose radiotherapy alone.

Some interventional procedures can result in very high x-ray doses. Potential biological effects of high x-ray doses are reviewed. Deterministic and stochastic effects in skin, bone, parotid glands, and lung are discussed. Threshold doses for the effects and relevant dosimetric principles are addressed. General principles for minimizing the potential for these effects are presented. Knowledge about these effects and the means to minimize radiation dose can assist the physician in the care of patients undergoing lengthy invasive radiologic procedures.

Purpose: To review the results of treatment with radiotherapy alone in 152 patients with adenocarcinoma of the endometrium who had medical or surgical contraindications to hysterectomy., Methods and Materials: We reviewed the records of all patients who were treated with radiotherapy alone for uterine carcinoma at The University of Texas M. D. Anderson Cancer Center between 1960 and 1986. One hundred fifty-two cases were analyzed. Most patients had multiple medical problems. One hundred sixteen patients were treated with intracavitary radiotherapy alone. A combination of external beam and intracavitary radiotherapy was used for 10 patients with Stage I disease who had unusually large cavities, 10 patients with Stage II disease, and 13 of 15 patients with Stage III or IV disease. Histologic material was reviewed in 91 cases., Results: Ten years after treatment, these patients were twice as likely to have died of intercurrent illness as of uterine cancer. The 5-year disease-specific survival rate of patients with Stage I disease was 87%. The disease-specific survival of patients with Stage II disease was 88%, which was not significantly different from that of Stage I patients. Stage III and IV patients had a significantly poorer disease-specific survival rate of 49% at 5 years. Intrauterine recurrence occurred in 14% of the patients with Stage I or II disease. Salvage treatment was attempted in 5 of the 10 patients who had isolated intrauterine recurrences of Stage I disease and was successful in all cases. Extrauterine pelvic recurrence developed in only 3% of Stage I and II patients. Of 82 Stage I and II carcinomas that were available for pathologic review, 17 (21%) were clear-cell or papillary serous variants. The disease-specific survival rate of patients with Stage I or II papillary serous carcinomas was 43%, significantly poorer than that of patients with endometrioid carcinomas. Seven patients experienced acute anesthesia-related complications; none were fatal. Five patients had serious late complications of radiation therapy., Conclusion: Radical radiotherapy achieved acceptable DSS and local control rates in patients with medically or surgically inoperable uterine carcinoma. However for patients with localized disease, such treatment is justified only when the operative risk exceeds the 10-15% uterine recurrence rate expected with radiation alone.

Between July 1986 and February 1991, 10 patients with small cell carcinoma of the cervix were prospectively treated with combination chemotherapy using cisplatin (50 mg/m2) and doxorubicin (50 mg/m2) on Day 1 and etoposide (75 mg/m2) on Days 1-3. All patients underwent an extensive pretreatment metastatic survey and had histologic confirmation of small cell carcinoma prior to entry in the study. Seven patients had stage Ib, 1 stage IIa, and 2 stage IIb. Nine patients received chemotherapy at primary presentation and 1 was treated for recurrent disease. In 6 cases, chemotherapy was given and then followed by radiation therapy. Three patients received chemotherapy following radical hysterectomy and 1 was treated for persistent disease after radiation therapy. Patients received a median of four courses of chemotherapy (range 2-6). Neutropenia was the dose-limiting toxicity with 9 of 10 patients requiring a dose reduction. There was no instance of neutropenic sepsis or other major toxicity. Seven patients had measurable disease at the start of therapy. Three of these patients had a complete clinical response, 1 had a partial response, 2 had stable disease, and 1 had progressive disease (response rate = 57%). The median survival was 28 months. At the time of this report, 4 of 6 patients with stage Ib cancers given primary treatment on this regimen remained free of disease (with 28 months the median follow-up). Our pilot study indicates that this chemotherapy regimen has activity in small cell carcinoma of the cervix and should be further evaluated as an adjuvant to surgery or radiation in patients with early stage disease.

A computer software tool has been developed to aid the treatment planner in selecting beam weights for three-dimensional radiotherapy treatment planning. The program consists of a feasibility search algorithm embedded in an interactive, user-friendly driving program. The feasibility search algorithm is based on the iterative relaxation algorithm of Cimmino [La Ricerca Scientifica, Vol. I, pp. 326-333 (1938)] as applied to the radiotherapy inverse problem by Altschuler et al. [Med. Phys. 13, 590 (1986)]. Relative importances of structures based upon clinical considerations can be incorporated into the algorithm. In order to speed convergence, the relaxation parameter is made to vary, with its value based upon a measure of deviation from feasibility. The interactive driving program is designed so that the treatment planner can make reasonable judgments regarding the acceptability of a plan in the event that the dose constraints yield no feasible solution. An example of the use of this program applied to a problem in three-dimensional radiotherapy treatment planning is illustrated.