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Purpose To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. Results The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa_R, Adnexa_L, Prostate, SeminalVesc, PenileBulb, Femur_R, and Femur_L. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Conclusions Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.

Background Limited data exist regarding the radiographic and histologic response of soft tissue sarcoma (STS) to neoadjuvant radiotherapy (RT). Methods Between February 2000 and January 2009, a total of 25 patients aged >16 years with intermediate- or high-grade primary STS of all sites were treated with neoadjuvant RT followed by definitive resection. Patients receiving chemoradiotherapy were excluded. Cross-sectional images obtained before and after RT as well as pathologic specimens were reviewed for maximal change in tumor diameter and percentage tumor necrosis, respectively. Clinicopathologic variables were analyzed for their association with pathologic and radiographic response. Results There were 18 extremity (72%) and 7 retroperitoneal (28%) tumors. Median maximal tumor size was 9 cm (range, 3.3–35 cm), and 88% were of high grade. There were 21 R0 resections (84%) and 4 R1 resections (16%). Radiographically, the median percentage change in tumor diameter was 0% (range, −25 to +86%). By Response Evaluation Criteria in Solid Tumors (RECIST), 5 patients demonstrated progressive disease, 20 demonstrated stable disease, and 0 demonstrated partial/complete response. The median pathologic percentage tumor necrosis was 30% (range, 5–100%). Two tumors (8%) demonstrated near-complete pathologic response (≥95% necrosis). Near-complete pathologic response was associated with favorable oncologic outcomes, although these associations were not statistically significant. Conclusions Radiologic and near-complete pathologic responses are rare events after preoperative RT for STS. Near-complete pathologic response may be a potentially meaningful surrogate marker for disease outcome and is not predicted by RECIST response. Knowledge of these historical response rates is important for the evaluation of novel neoadjuvant therapies for patients with STS.

Purpose: We defined the efficacy of radiotherapy for the treatment of high grade (Gleason scores 8 to 10) adenocarcinoma of the prostate.Materials and Methods: A total of 50 patients underwent radiotherapy with curative intent for clinically localized prostate cancer with Gleason scores of 8 to 10 at 1 of 4 facilities affiliated with the University of California San Francisco. Patients were considered to have biochemical failure if they had a significant increase in prostate specific antigen (PSA) of 0.5 ng./ml. per year, an increase in PSA to greater than 1.0 ng./ml. or a positive biopsy.Results: Among the 50 patients median PSA was 22.7 ng./ml. (range 1.3 to 93.4). Tumors were clinical stage T1 or T2 in 46 percent of the cases and stage T3 or T4 in 54 percent. The overall actuarial probability of freedom from biochemical failure at 4 years was 23 percent. In a multivariate analysis including all patients pretreatment PSA was the only predictor of PSA failure, with 64 percent free of progression ...

Purpose: A preliminary study was undertaken to determine whether the addition of a collagen gel in the formulation of cisplatin for intratumoral administration of cisplatin affected platinum plasma concentrations. A second study was undertaken to determine the local effects of intratumoral administration of cisplatin mixed with collagen given concurrently with irradiation. Methods and Materials: Twelve dogs with advanced stage tumors were administered a dose of 0.25 mg of cisplatin per kg of body weight intratumorally with or without collagen using a two-period crossover design. Twelve additional dogs received concurrent irradiation (48 Gy) delivered in 12 fractions over 4 weeks and intratumoral cisplatin chemotherapy given the first day of each week at a dose of 0.5 mg of cisplatin per cm 3 of tissue. Results: The cumulative cisplatin plasma concentrations varied over time from dog to dog, but the use of collagen in the formulation significantly reduced the systemic exposure of cisplatin. For the dogs given intratumoral cisplatin and irradiation, complete responses were observed in 10 dogs. Seven dogs had local recurrence. One dog had tumor recurrence in the radiochemotherapy field and six dogs had recurrence at the margin of the radiochemotherapy field, but within the irradiation field. Normal tissue reactions were similar in the radiochemotherapy field and in the margin treated with radiation only. Cumulative effect of repeated intratumoral administration on plasma concentration of cisplatin was not observed. Conclusions: These findings provide support for an extended investigation of this combined regimen. The lack of systemic toxicity associated with intratumoral administration of cisplatin mixed with collagen may allow a safe clinical evaluation of the interaction between cisplatin and radiation.

Cervical cancer is one of the most common cancers affecting women, with most early disease treated with either surgery or radiation alone with an 85%–95% 5-year survival rate, while locally advanced cervical cancer (LACCA) requires multiple therapeutic modalities. The clear distinction between early and LACCA has, in recent years, blurred as stages IB2 and bulky IIA, which were traditionally thought of as early disease, have been shown to require more treatment than other early stage cervical cancer. LACC is now treated with cisplatin-based chemoradiation therapy based upon the results of the randomized co-operative group studies that demonstrated reduced relative risk of death, local failure rates, and incidence of distant metastases. Recurrent cervical cancer is devastating and is rarely cured. Treatment of recurrent cervical carcinoma depends on the previous therapy, the site of recurrence, and the extent of the recurrence. This review will outline the treatment options for the various stages of cervical cancer.

Fourteen patients whose augmented or reconstructed breasts were treated with radiation therapy were analyzed. Silicone gel implants were used in 13 patients and free-injected silicone in one patient. The total radiation dose ranged from 4400 to 6200 cGy using tangential photon fields or an en face electron field by megavoltage equipment. In several cases, electron boost radiation was added to the tumor bed. The majority of the patients tolerated therapy well with minimal transient skin reactions; only three patients required a treatment break secondary to moist desquamation. Three patients developed documented implant encapsulation, although the majority retained good to excellent cosmesis. In summary, when breast carcinoma arises in the augmented or reconstructed breast, conservative management (i.e., limited surgery and definitive irradiation) is feasible without compromising the therapy or the cosmetic result. Thus, conservative management should be offered as an option to patients who are interested in breast prosthesis conservation.

Primary clear cell adenocarcinoma of the rectovaginal septum is rare and typically emerges in the setting of endometriosis. We report a case of a 52-year-old woman with clear cell adenocarcinoma of the rectovaginal septum presenting with vaginal hemorrhage. Management with concurrent chemoradiation with cisplatin and paclitaxel is discussed. Six years following the completion of treatment, the patient is without evidence of disease or significant long-term toxicity

Purpose This multicentered phase III trial was designed to compare an emulsion containing trolamine against the usual supportive care within each participating institution for patients with head and neck cancer undergoing radiation therapy. Patients and Methods Patients with biopsy-proven squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx were randomly assigned to one of the following treatments: prophylactic trolamine emulsion, interventional trolamine emulsion, or declared institutional preference. The primary outcome was the reduction in grade 2 or higher skin toxicity, as per National Cancer Institute Common Toxicity Criteria version 2.0. Secondary outcomes included patient-reported quality of life (QOL). Results From October 2000 to April 2002, 547 patients from 51 institutions were entered onto the trial. The average age was 59 years. Patients were predominately male (79%) and most continued to use tobacco products (52%). The rates of grade 2 or higher radiation dermatitis were 79%, 77%, and 79% in the prophylactic, interventional, and institutional preference arms of the study, respectively. No significant differences in QOL were found. Conclusion The results of this trial demonstrate no advantage for the use of trolamine in reducing the incidence of grade 2 or higher radiation dermatitis or improving patient-reported QOL. The use of 15 different local standards of care highlights the need to continue research that will result in evidence-based recommendations to reduce the burden of radiation dermatitis.

Objectives. We had previously reported an association between the use of recombinant human erythropoietin (rHuEPO) and thrombosis in patients with cervix and vulvo-vaginal cancer treated with chemotherapy and radiation. We hypothesized that low-dose warfarin would be effective prevention for thromboembolic events in this setting. Methods. A retrospective analysis of patients with cervical or vulvo-vaginal carcinoma receiving chemoradiation and rHuEpo was performed. Thirty-two patients received rHuEpo alone, and 24 received warfarin (1–2 mg) and rHuEpo. The primary endpoint was objectively proven symptomatic venous thrombosis. Results. There was no difference in the baseline characteristics (e.g. age, stage, body mass index, mean and peak hemoglobin, WBC and platelet counts, and number of transfusions) between these two groups. The rate of thrombosis also was not statistically different ( P = 0.62). Nine of 24 patients had a symptomatic deep vein thrombosis (DVT) while receiving warfarin compared to 10 of 32 patients not on warfarin. There was no difference between the two groups in the percentage of patients with upper extremity DVT ( P = 0.83) or lower extremity DVT ( P = 0.64). Conclusion. Daily low-dose warfarin did not alter the incidence of symptomatic DVT in patients with cervical or vulvo-vaginal cancer who received rHuEpo in conjunction with chemoradiation.

To determine the feasibility and a recommended phase II dose of tirapazamine when combined with chemoradiotherapy in limited-stage small cell lung cancer (LSCLC).Concurrent chemoradiotherapy consisted of two cycles of cisplatin, etoposide, and once-daily radiation to 61 Gy. Tirapazamine (260 mg/m2) was given 1 h before cisplatin with planned dose escalation to 330 mg/m2 in the absence of dose-limiting toxicity, defined asor =33% esophagitis (grade 3 or above). Consolidation therapy consisted of two cycles of tirapazamine (330 mg/m2), cisplatin, and etoposide. Complete responders received prophylactic cranial irradiation.Thirty patients were enrolled at the 260 mg/m2 tirapazamine dose. All had performance status of 0-1. By comparison with S9713, a predecessor Southwest Oncology Group study in LSCLC that used the same concurrent chemoradiotherapy without tirapazamine, the present trial showed a higher rate of grade 3-4 esophagitis (34% versus 22%), vomiting (34% versus 23%), and febrile neutropenia (7% versus 2%). The consolidation phase was relatively well tolerated, with grade 4 neutropenia in 44% and febrile neutropenia in 5% of patients. There were two treatment-related deaths: one from neutropenic fever and one from respiratory infection. The overall response rate was 80%, and the median survival was 22 months.Protocol-defined dose-limiting toxicity was observed at the initial tirapazamine dose, precluding dose escalation. Compared with S9713, the addition of tirapazamine increased the incidence of vomiting, neutropenia, and febrile neutropenia, although the overall toxicity profile remained acceptable. In view of the observed favorable survival, further study of tirapazamine in LSCLC is warranted.

BACKGROUND Because studies have suggested that anemia has an adverse effect on outcome for patients with cervical carcinoma who are treated with radiation, recombinant human erythropoietin (rHuEpo) has been used increasingly to maintain hemoglobin levels in these patients. Erythropoietin may increase the risk of thrombosis. The authors performed a retrospective analysis to determine whether there was an increased rate of symptomatic venous thrombosis associated with the use of rHuEpo in patients with carcinoma of the uterine cervix and vagina. METHODS A retrospective, case–control study was performed on consecutive patients with localized carcinoma of the uterine cervix or vagina who were treated with chemotherapy and radiation (chemoradiotherapy). The primary outcome was symptomatic venous thrombosis. RESULTS One hundred forty-seven patients were reviewed. When they were divided into women who received rHuEpo (n = 75 patients) and women who did not receive rHuEpo (n = 72 patients), there were no significant differences in age, height, weight, disease stage, or body mass index. Fewer patients in the rHuEpo group required transfusions. In the rHuEpo group, 17 of 75 patients had either an upper extremity thrombosis (n = 12 patients) or a lower extremity thrombosis (n = 7 patients): 2 patients had both, and 2 patients had more than 1 event. Two of 72 patients who did not receive rHuEpo had symptomatic thrombosis. Patients who received rHuEpo had an odds ratio (OR) of developing thrombosis of 10.3 (95% confidence interval [95% CI], 2.3–46.2). Multiple logistic regression revealed that only the use of rHuEpo was associated with an increased risk of thrombosis (OR, 15.3; 95% CI, 3.1–76.7). CONCLUSIONS Patients with cervical carcinoma who received chemoradiotherapy and rHuEpo had an increased risk of symptomatic venous thrombosis. Cancer 2003;98:1514–20. © 2003 American Cancer Society. DOI 10.1002/cncr.11700

To determine the incidence of thrombosis associated with administration of rHuEpo, the authors conducted a retrospective study of patients who were being treated for cervical or vaginal cancer who did and did not receive rHuEpo. From a review of consecutive medical records of the University of California-Davis Cancer Center between 1994 and 2002, a cohort of 147 patients with nonmetastatic cervical carcinoma (squamous cell carcinoma, n = 130; adenocarcinoma, n = 15; or adenosquamous histology, n = 2) or vaginal carcinoma (squamous cell; n = 3) who were receiving combined, concurrent chemotherapy and radiation were identified. The patients were divided into 2 groups, those who received rHuEpo and those who did not, and all indications or objective diagnoses of upper and/or lower extremity thrombosis were recorded. As a rule, patients at UC Davis Cancer Center whose hemoglobin counts dropped below 11.0 gm/dL received transfusions of packed red blood cells. After mid-1999, it became routine to treat patients with Hb levels of 12.0 gm/dL or less with rHuEpo to decrease the numbers of transfusions necessary. Initially, rHuEpo was given in doses of 10,000 IU 3 times a week; this was later modified to 20,000 IU twice a week. There were 75 patients who received rHuEpo and 72 who did not. There were no significant differences in demographic or clinical characteristics between the 2 groups. Chemotherapy consisted of a combination of 5-fluorouracil and cisplatin, except for 4 patients who received only 5-fluorouracil, and was universally administered through indwelling central venous catheters. Patients generally received daily radiotherapy with a total of 4500 cGy administered to the pelvis plus a total of 3000 cGy of intracavitary radiation therapy. There were fewer transfusions necessary in the rHuEpo group than in the nonrHuEpo group (23 of 75 compared with 31 of 72, respectively; P = .007). Seventeen of the 75 women receiving rHuEpo (23%) developed symptomatic venous thrombosis, 12 in the upper extremities and 2 in the lower extremities, compared with 2 (1 in the upper and 1 in the lower extremity) of 72 women (2.8%) who did not receive rHuEpo (P = .003). The risk of developing upper-extremity thrombosis was considerably greater for those taking rHuEpo compared with those not taking rHuEpo (odds ratio 14.5; 95% confidence interval; P = .001). There was a less significant risk for lower-extremity thrombosis. After multivariate logistic analyses of known risk factors, including rHuEpo administration, age, body mass index, and mean Hb levels, only rHuEpo remained a significant predictor for upper extremity thrombosis (odds ratio 9.3; 95% confidence interval; P = .007).