Pelvic Tumor Control Research Articles

Lumbar functional evaluation of pelvic bone sarcomas after surgical resection and spinal pelvic fixation: A clinical study of 304 cases.

We endeavored to introduce a novel scoring system (Lumbar Functional Index, LFI) capable of evaluating lumbar function in pelvic bone sarcoma patients who underwent surgical resection and spinal pelvic fixation, while simultaneously identifying the incidence, outcomes, and risk factors of lumbar function impairment among these populations. A cohort of 304 primary bone sarcoma patients were recruited. The LFI was created based on the Oswestry Dysfunction Index (ODI) and Japanese Orthopaedic Association (JOA) scores. Lumbar function impairment was defined as LFI score ≥ 18 points, which was identified as high LFI. Demographic data, clinical characteristics, and oncological outcomes were analyzed. The cohort included chondrosarcoma (39.8%), osteosarcoma (29.9%), Ewing sarcoma (8.6%), bone-derived undifferentiated pleomorphic sarcoma (7.2%), giant cell tumor of bone (7.2%), chordoma (2.3%), and other bone sarcomas (5.0%). The LFI score exhibited significant negative correlation with common scoring systems of bone sarcoma. The incidence of high LFI was 23.0%. Patients with high LFI demonstrated a higher prevalence of type I + II + III + IV pelvic tumor, more sacrificed nerve roots and bilateral lumbar spine fixation during surgery, while lower percentage of R0 resection and local control of pelvic tumor. Decreased median overall survival (30 vs. 52 months, p < 0.001) and recurrence-free survival (14 vs. 24 months, p < 0.001) time were observed in these patients. Type I + II + III + IV pelvic tumor and sacrificed nerve roots≥2 were identified as risk factors for high LFI, while R0 resection and local control were identified as protective factors. The LFI scoring system exhibited a significant negative correlation to current scoring systems. High LFI patients had worse prognosis and distinct characteristics. The risk factors of high LFI included type I + II + III + IV pelvic tumor and sacrificed nerve roots≥2, and the protective factors included R0 resection and local control.

Long-Term Outcomes of NRG Oncology/RTOG 0529: A Phase 2 Evaluation of Dose-Painted Intensity Modulated Radiation Therapy in Combination With 5-Fluorouracil and Mitomycin-C for the Reduction of Acute Morbidity in Anal Canal Cancer

A multi-institutional phase 2 trial assessed long-term outcomes of dose-painted intensity modulated radiation therapy (IMRT) with 5-fluorouracil (5FU) and mitomycin-C (MMC) for anal canal cancer. T2-4N0-3M0 anal cancers received 5FU (1000 mg/m2/d, 96-hour infusion) and MMC (10 mg/m2 bolus) on days 1 and 29 of dose-painted IMRT prescribed as follows: T2N0=42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes, 28 fractions; T3-4N0-3=45Gy elective nodal, 50.4 Gy ≤3 cm and 54 Gy >3cm metastatic nodal and 54 Gy anal tumor planning target volumes, 30 fractions. Local-regional failures, distant metastases, and colostomy failures were assessed using the cumulative incidence method, and disease-free survival, overall survival, and colostomy-free survival were assessed using the Kaplan-Meier method. Late effects were scored using National Cancer Institute-Common Terminology Criteria for Adverse Events v3. Of 52 patients, 54% were stage II, 25% were stage IIIA, and 21% were stage IIIB. Median follow-up was 7.9 years (min-max, 0.02-9.2 years). Local-regional failure, colostomy failures, distant metastases, overall survival, disease-free survival, and colostomy-free survival at 5 years are 16% (95% confidence interval [CI], 7%-27%), 10% (95% CI, 4%-20%), 16% (95% CI, 7%-27%), 76% (95% CI, 61%-86%), 70% (95% CI, 56%-81%), and 74% (95% CI, 59%-84%); and at 8 years they are 16% (95% CI, 7%-27%), 12% (95% CI, 5%-23%), 22% (95% CI, 12%-34%), 68% (95% CI, 53%-79%), 62% (95% CI, 47%-74%) and 66% (95% CI, 51%-77%), respectively. Eight patients experienced local-regional failure, with 5 patients having persistent disease at 12 weeks. No isolated nodal failures occurred in the microscopic elective nodal volumes. Six patients required colostomy-5 for local-regional salvage and 1 for a temporary ostomy for anorectal dysfunction. Rates of late adverse events included: 28 patients (55%) with grade 2, 8 patients (16%) with grade 3, 0 patients with grade 4, and 2 patients (4%) with grade 5 events (sinus bradycardia and myelodysplasia, possibly owing to chemotherapy). Only 11 patients reported grade 1 to 3 sexual dysfunction. Dose-painted IMRT with 5FU/MMC for the treatment of anal canal cancer yields comparable long-term efficacy as conventional radiation cohorts. Enhanced normal tissue protection lowered rates of grade 3 and higher late effects without compromising pelvic tumor control.

PO21: Racial Disparities in the Receipt of Brachytherapy for Cervical Cancer and the Impact on Patient Outcome

Purpose: The standard of care treatment for locally advanced cervical cancer is concurrent chemoradiation followed by brachytherapy. Brachytherapy is a critical part of treatment and is associated with improved patient survival and pelvic tumor control. In this study, we investigated whether differences exist in the receipt of brachytherapy among racial groups.

Efficacy and toxicity of postoperative external beam radiotherapy or chemoradiation for early-stage cervical cancer

ObjectiveThe aim of this study was to assess the impact of the evolving role of the addition of chemotherapy to postoperative radiotherapy on oncological outcomes and toxicity in patients with...

Assessment of a Watch-and-Wait Strategy for Rectal Cancer in Patients With a Complete Response After Neoadjuvant Therapy

The watch-and-wait (WW) strategy aims to spare patients with rectal cancer unnecessary resection. To analyze the outcomes of WW among patients with rectal cancer who had a clinical complete response to neoadjuvant therapy. This retrospective case series analysis conducted at a comprehensive cancer center in New York included patients who received a diagnosis of rectal adenocarcinoma between January 1, 2006, and January 31, 2015. The median follow-up was 43 months. Data analyses were conducted from June 1, 2016, to October 1, 2018. Patients had a clinical complete response after completing neoadjuvant therapy and agreed to a WW strategy of active surveillance and possible salvage surgery (n = 113), or patients underwent total mesorectal excision and were found to have a pathologic complete response (pCR) at resection (n = 136). Kaplan-Meier estimates were used for analyses of local regrowth and 5-year rates of overall survival, disease-free survival, and disease-specific survival. Compared with the 136 patients in the pCR group, the 113 patients in the WW group were older (median [range], 67.2 [32.1-90.9] vs 57.3 [25.0-87.9] years, P < .001) with cancers closer to the anal verge (median [range] height from anal verge, 5.5 [0.0-15.0] vs 7.0 [0.0-13.0] cm). All 22 local regrowths in the WW group were detected on routine surveillance and treated by salvage surgery (20 total mesorectal excisions plus 2 transanal excisions). Pelvic control after salvage surgery was maintained in 20 of 22 patients (91%). No pelvic recurrences occurred in the pCR group. Rectal preservation was achieved in 93 of 113 patients (82%) in the WW group (91 patients with no local regrowths plus 2 patients with local regrowths salvaged with transanal excision). At 5 years, overall survival was 73% (95% CI, 60%-89%) in the WW group and 94% (95% CI, 90%-99%) in the pCR group; disease-free survival was 75% (95% CI, 62%-90%) in the WW group and 92% (95% CI, 87%-98%) in the pCR group; and disease-specific survival was 90% (95% CI, 81%-99%) in the WW group and 98% (95% CI, 95%-100%) in the pCR group. A higher rate of distant metastasis was observed among patients in the WW group who had local regrowth vs those who did not have local regrowth (36% vs 1%, P < .001). A WW strategy for select rectal cancer patients who had a clinical complete response after neoadjuvant therapy resulted in excellent rectal preservation and pelvic tumor control; however, in the WW group, worse survival was noted along with a higher incidence of distant progression in patients with local regrowth vs those without local regrowth.

1404 SUBSTANTIAL PELVIC RECURRENCE(PR) RATES AFTER CONTEMPORARY RADICAL CYSTECTOMY (RC) FOR PT3/4 N0-2 TRANSITIONAL BLADDER CANCER(TBC): A MULTIINSTITUTIONAL CANADIAN STUDY

You have accessJournal of UrologyBladder Cancer: Invasive I1 Apr 20121404 SUBSTANTIAL PELVIC RECURRENCE(PR) RATES AFTER CONTEMPORARY RADICAL CYSTECTOMY (RC) FOR PT3/4 N0-2 TRANSITIONAL BLADDER CANCER(TBC): A MULTIINSTITUTIONAL CANADIAN STUDY Libni Eapen, Rodney Breau, Eric Belanger, and Scott Morgan Libni EapenLibni Eapen Ottawa, Canada More articles by this author , Rodney BreauRodney Breau Ottawa, Canada More articles by this author , Eric BelangerEric Belanger Ottawa, Canada More articles by this author , and Scott MorganScott Morgan Ottawa, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1855AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The risk of developing PR either alone,or in addition to distant metastases(DM) following RC for pT3/4 TBC is not well characterized. This is due to inconsistent pelvic imaging in patients with recurrent cancer post RC, especially once distant metastases develop. Our objective was to determine the risk of PR in patients undergoing contemporary RC for pT3/4 TBC across Canada. METHODS Canadian academic cancer centres were solicited to contribute to the study which is an individual case audit of a sample of RC done at each institution. At each center a urologist,radiation oncologist and pathologist reviewed the cases.The pathologist generated a list of all RC done IN SEQUENCE starting Jan 1/2005.In order to avoid selection bias the first 10 consecutive patients (pts) meeting the following selection criteria were submitted REGARDLESS of wether PR status was known: pT3/4 N0-2 M0 TBC and no preop or adjuvant XRT. Neo or adjuvant chemo was permitted. Collected data included: age, date of RC, stage, #nodes, date of last follow up, and status (no PR, PR only, PR and DM, DM only, or pelvic status unknown) Kaplan Meier actuarial risks of pelvic recurrence (ARPR) were calculated. RESULTS Nine centres from six provinces provided data on 105 pts. Age range 43.2-91.4 Mean/Median 68.7/69.9 years.T stage was pT3=76 (pT3a=36, pT3b=39, PT3NOS=1) and pT4=29 (pT4a=26, pT4b=2, pT4NOS=1). N stage was N0=57, N1=14, N2=26 and Nx=8. # nodes dissected ranged from 0-67 with Mean/Median = 12/11. >15 nodes=29.8%, 11-15=20.2%, 6-10=23.1% and 26.9% =5 or less. Followup: range 0.2-74.6 months, median=13.1. 37 pts had PR, 52 pts had no PR and pelvic status was unknown in 16pts but were considered to have no PR. Of the 37 pts with PR 24 also developed DM and 13 had only PR. At 2 years the ARPR was: all 105 pts= 51% (95%CI 38-63%), pT3 pts=50% (95% CI 36-64%), pT3a=40% pT3b=68%, pT4 pts=54% (95% CI 29-80%), pT4a=55% pT4b=50%. CONCLUSIONS Patients with pT3/4 N0-2 TBC have a high rate of PR after RC and major node dissection. Whilst pelvic tumor eradication may not be sufficient to cure a patient (owing to DM) it is nevertheless necessary whenever cure is sought.Increasing the cure rate in these pts requires both better treatment of systemic distant metastases and improved pelvic tumor control. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e570 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Libni Eapen Ottawa, Canada More articles by this author Rodney Breau Ottawa, Canada More articles by this author Eric Belanger Ottawa, Canada More articles by this author Scott Morgan Ottawa, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Radiotherapy and Hyperthermia for Treatment of Primary Locally Advanced Cervix Cancer: Results in 378 Patients

To report response rate, pelvic tumor control, survival, and late toxicity after treatment with combined radiotherapy and hyperthermia (RHT) for patients with locally advanced cervical carcinoma (LACC) and compare the results with other published series. From 1996 to 2005, a total of 378 patients with LACC (International Federation of Gynecology and Obstetrics Stage IB2-IVA) were treated with RHT. External beam radiotherapy (RT) was applied to 46-50.4 Gy and combined with brachytherapy. The hyperthermia (HT) was prescribed once weekly. Primary end points were complete response (CR) and local control. Secondary end points were overall survival, disease-specific survival, and late toxicity. Patient, tumor, and treatment characteristics predictive for the end points were identified in univariate and multivariate analyses. Overall, a CR was achieved in 77% of patients. At 5 years, local control, disease-specific survival, and incidence of late toxicity Common Terminology Criteria for Adverse Events Grade 3 or higher were 53%, 47%, and 12%, respectively. In multivariate analysis, number of HT treatments emerged as a predictor of outcome in addition to commonly identified prognostic factors. The CR, local control, and survival rates are similar to previously observed results of RHT in the randomized Dutch Deep Hyperthermia Trial. Reported treatment results for currently applied combined treatment modalities (i.e., RT with chemotherapy and/or HT) do not permit definite conclusions about which combination is superior. The present results confirm previously shown beneficial effects from adding HT to RT and justify the application of RHT as first-line treatment in patients with LACC as an alternative to chemoradiation.

Comparison of high-dose-rate and low-dose-rate brachytherapy in the treatment of endometrial carcinoma

To compare the outcomes for endometrial carcinoma patients treated with either high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy. This study included 1,179 patients divided into LDR (1,004) and HDR groups (175). Patients with International Federation of Gynecology and Obstetrics (FIGO) surgical Stages I-III were included. All patients were treated with postoperative irradiation. In the LDR group, the postoperative dose applied to the vaginal cuff was 60-70 Gy surface doses to the vaginal mucosa. The HDR brachytherapy prescription was 6 fractions of 2 Gy each to a depth of 0.5 cm from the surface of the vaginal mucosa. Overall survival, disease-free survival, local control, and complications were endpoints. For all stages combined, the overall survival, disease-free survival, and local control at 5 years in the LDR group were 70%, 69%, and 81%, respectively. For all stages combined, the overall survival, disease-free survival, and local control at 5 years in the HDR group were 68%, 62%, and 78%, respectively. There were no significant differences in early or late Grade III and IV complications in the HDR or LDR groups. Survival outcomes, pelvic tumor control, and Grade III and IV complications were not significantly different in the LDR brachytherapy group compared with the HDR group.

HIV impact on acute morbidity and pelvic tumor control following radiotherapy for cervical cancer

Objective. To determine the impact of HIV infection on acute morbidity and pelvic tumor control following external beam radiotherapy (EBRT) for cervical cancer. Method. 218 patients receiving EBRT who also had HIV testing after informed consent was obtained were evaluated. Acute treatment toxicity was documented weekly during treatment and 1 month post-EBRT. Pelvic tumor control was documented at 4 and 7 months post-EBRT. Clinicians were blinded for HIV results. Results. About 20% of the patients were HIV-positive. Overall, 53.4% of the patients had radiation-related acute toxicity (grade 3–4). HIV infection was associated with a 7-fold higher risk of multisystem toxicity: skin, gastrointestinal tract (GIT) and genitourinary tract (GUT) systems. It was also an independent risk factor for treatment interruptions (adjusted relative risk 2.2). About 19% of the patients had residual tumor at 4 and 7 months post-EBRT. HIV infection was independently and significantly associated with 6-fold higher risk of residual tumor post-EBRT. The hazard ratio of having residual tumor after initial EBRT was 3.1-times larger for HIV-positive than for HIV-negative patients ( P = 0.014). Conclusion. HIV is associated with increased risk of multisystem radiation-related toxicity; treatment interruptions and pelvic failure (residual tumor) following EBRT. HIV infection is an adverse prognostic factor for outcome of cervical cancer treatment.

Microcirculation MR imaging for the prediction of long-term outcome in cervical cancer

5025 Background: The ability to predict efficacy prior to or early during the course of a therapeutic modality can lead to improved outcome by avoiding ineffectual therapies. The purpose of this study was to test if in-vivo functional MR imaging can, by reflecting microcirculatory response of tumor to cytotoxic therapy, predict failure early during the course of treatment in cervical cancer. Methods: One-hundred and one patients with cervical cancer stages IB2-IV treated with radiation/chemotherapy (RT/CT) underwent Dynamic Contrast Enhanced (DCE) MRI before (1st MRI) and during RT at 2 weeks (2nd MRI) and 4 weeks of RT (3rdMRI). Mean follow up was 4.9 years (1.5–8.0 years). Pelvic tumor control and disease-free survival were correlated with imaging parameters derived from the time/signal-intensity curve of the DCE-MRI of each tumor pixel. These included the signal intensity (SI) of the plateau phase (SIp), the lowest 2.5th and 5.0th percentiles of the entire tumor pixels (SI 2.5 and SI 5.0), the slope of...

Brachytherapy management of the retroverted uterus using ultrasound-guided implant applicator placement

Purpose Patients with a retroverted uterus present a dilemma for brachytherapy in gynecologic malignancies because of the challenges of the procedure and the risk of uterine perforation. The purpose of this study was to evaluate the efficacy and outcome of ultrasound-guided brachytherapy applicator placement and intraoperative uterine anteversion in patients with gynecologic malignancies, who have a retroverted uterus. Methods and materials Thirty-three brachytherapy insertions were performed in 18 patients with retroverted uterus (cervical cancer, 17; vaginal cancer, 1). The endocervical canal was dilated, the intrauterine Fletcher tandem was inserted in retroverted fashion and then anteverted along with the uterus under continuous ultrasound guidance. The anteverted tandem position was secured with vaginal packing and use of a second and/or third flange on the tandem stem. Treatment was delivered with low-dose-rate brachytherapy using afterloading with 137Cs. Brachytherapy was combined with external beam radiation in all patients. Median post-therapy follow-up was 2.17 years (range, 0.75–9.25 years). Results Procedure. Ultrasound-guided dilation of the cervix was achieved in all procedures. Sounding of the retroverted uterus up to the fundus was accomplished successfully in all but one procedure (because severe retroflexion of the uterus and fixation of the fundus to the sacrum). Ultrasound-guided anteversion of the inserted tandem and uterus was achieved in all procedures. No ultrasonographic evidence of perforation was seen in any of the procedures. Intraoperative radiographs showed satisfactory position of the applicators in 31 of the 33 procedures; 2 cases were re-packed resulting in acceptable final applicator position. No backward rotation of the tandem was observed over the duration of the low-dose-rate brachytherapy application. The mean ratio between the dose to the rectum and Point A was 73%; the ratio between the dose to the bladder and Point A was 76%. Outcome. In the 17 patients with cervical cancer, 2-year pelvic tumor control rate was 100%, and 2-year actuarial disease-free survival was 73%. The patient with vaginal cancer has no evidence of disease 5 months post-therapy. There was one complication (1/18 patients, 5.5%): a rectal stricture in a patient with stage IVA cervical cancer requiring colostomy. Conclusions The use of ultrasound-guided uterine anteversion for brachytherapy applicator placement is feasible and results in acceptable outcome and complication rates in a population otherwise difficult to manage and at high risk for uterine perforation. Based on these results, this method is likely preferable to brachytherapy with a retroverted tandem, or to the omission of brachytherapy.

Long‐term results of high‐dose rate intracavitary brachytherapy for squamous cell carcinoma of the uterine cervix

The authors performed a long-term follow-up study to evaluate the efficacy and late toxicity of high-dose rate intracavitary brachytherapy (HDR-ICBT) for cervical carcinoma. From 1968 to 1986, 1148 patients with Stage IB to IVB squamous cell carcinoma of the cervix (staging was performed according to the International Federation of Gynecology and Obstetrics) were treated with a combination of external beam radiotherapy (EBRT) and HDR-ICBT. For patients with early-stage disease, 20 gray (Gy) of EBRT was delivered to the whole pelvis, followed by 24 Gy/4 fractions of HDR-ICBT and 30 Gy of central-shielding EBRT. For patients with advanced-stage disease, 20-40 Gy of whole pelvic EBRT was administered, followed by 24 Gy/4 fractions of ICBT and 30-10 Gy of central-shielding EBRT. The overall treatment time was approximately 6 weeks. Among survivors, the follow-up rate was 98% and the median follow-up duration was 22 years. The 10-year pelvic tumor control rates were 93% for patients with Stage IB disease, 82% for patients with Stage II disease, and 75% for patients with Stage III disease. The 10-year overall and cause-specific survival rates were 74% and 89% for patients with Stage IB disease, 52% and 74% for patients with Stage II disease, and 42% and 59% for patients with Stage III disease, respectively. The 10-year actuarial rates of major complications were 4.4% in the rectosigmoid colon, 0.9% in the bladder, and 3.3% in the small intestines. The results of the current study suggest that the combination of EBRT and HDR-ICBT according to the authors' protocol provided outcomes that were comparable to those of the conventional low-dose rate brachytherapy with acceptable rates of late complications in the treatment of cervical carcinoma.

Patterns of treatment failure following radiotherapy with combination chemotherapy for patients with high-risk stage IIB cervical carcinoma.

To evaluate the patterns of treatment failure in patients with stage IIB cervical carcinoma with high-risk factors following radiotherapy given concurrently with combination chemotherapy. A retrospective analysis of 349 patients with stage IIB cervical carcinoma with high-risk factors (lesion size >/= 4 cm, lymph node metastasis, high-risk cell type) treated by radiotherapy and cisplatin-based chemotherapy was performed. Sites of treatment failure were categorized as pelvic, pelvic plus distant metastases, and distant metastases alone. Pelvic failure included local and pelvic nodal failures. Of the 349 patients, treatment failure occurred in 79 patients (22.6%). Forty-six (13.2%) had persistent disease and 33 (9.5%) had recurrent disease. Among these 79 patients, overall pelvic failure was observed in 67%, of whom 72% had local failure; 19%, pelvic nodal failure; and 9%, local with pelvic nodal failure. Incidences of distant metastases alone and pelvic with distant metastases were 24% and 9%. In the 26 patients with distant metastases either alone or combined with pelvic failure, the most frequent metastatic region was the paraaortic lymph node (50%). The distant metastasis rate was 6.5% (19/289) in the pelvic tumor control group and 11.6% (7/60) in the pelvic failure group. Pelvic failure was the most frequent failure in the group with tumor size of 4 cm or more, whereas, for the positive-lymph-node group, distant metastasis was most frequent and metastases to paraaortic lymph nodes were common. The incidences of pelvic failure alone and distant metastases were similar in the high-risk cell-type group, and the distant metastasis regions were mostly paraaortic lymph nodes. Although systemic chemotherapy was administered concurrently with radiotherapy, the incidence of pelvic failure was highest, followed by paraaortic lymph node metastases, in patients with stage IIB cervical carcinoma with high-risk factors, following radiotherapy with combination chemotherapy. To evaluate the patterns of treatment failure in patients with stage IIB cervical carcinoma with high-risk factors following radiotherapy given concurrently with combination chemotherapy.

Patterns of failure in carcinoma of the uterine cervix treated with definitive radiotherapy alone.

The purpose of this retrospective study was to evaluate the patterns of failure for the patients treated with definitive radiotherapy, and to discuss future treatment strategies for the uterine cervical cancer. From 1986 to 1995, 177 patients with stages I-III cervical cancer treated with a combination of two-axial conformal radiotherapy and radium brachytherapy were analyzed. The first treatment failures were pelvic failure in 11%, and distant metastases (DM) in 16% of the 177 patients. Paraaortic lymph nodes (PAN) were the most frequently metastatic regions (71%). In the pelvic control group, DM were in 6% of patients for stages I-II, and in 32% of patients for stage III. In the pelvic failure group, DM were in 75% of patients for stages I-II, and in 19% of patients for stage III. In stages I-II, the DM rate was significantly correlated with pelvic tumor control. However, there was no correlation in stage III. To improve survival, it is important to increase the pelvic tumor control rate for patients with stage I-II, and to increase the pelvic tumor and metastatic control rate in stage III. Additional treatments such as chemotherapy and/or PAN irradiation using conformal radiotherapy are required in stages I-II with locally bulky tumor and in stage III.

Long-term follow-up of RTOG 88-05: twice-daily external irradiation with brachytherapy for carcinoma of the cervix

Purpose: This is a long-term follow-up study to evaluate the efficacy and toxicity of twice-daily external irradiation to the pelvis with brachytherapy for carcinoma of the cervix. Materials and Methods: This study was designed to administer twice-daily irradiation doses of 1.2 Gy to the pelvis at 4- to 6-hour intervals, 5 days per week. The total external irradiation doses to the whole pelvis were 24 to 48 Gy. Irradiation therapy also included one or two low dose rate intracavitary implants to deliver a total minimum dose of 85 Gy to point A and 65 Gy to the lateral pelvic lymph nodes. Results: Eighty-one patients with clinical stages IB to IVA carcinoma of the cervix were enrolled in this study. Hyperfractionated external irradiation was completed in 88% (71 of 81). Brachytherapy was given in two implants in 46% (33 of 71) and 54% (38 of 71) had one implant. Six patients had acute grade 3 toxicities. The cumulative rates of grades 3 and 4 late effects for patients with stages IB2, IIA, and IIB disease were 7% at 3 years, 7% at 5 years, and 10% at 8 years. For patients with stages III and IVA disease, the late toxicities (grades 3 and 4) were 7% at 3 years and 12% at 5 years. The site of first failure was in the pelvis in 41% (33 of 81), para-aortic or supraclavicular lymph nodes in 6% (5 of 81), and other distant metastatic sites in 14% (11 of 81). The absolute survivals were 61% at 3 years, 48% at 5 years, and 45% at 8 years. The disease-free survivals were 43% at 3 years, 38% at 5 years, and 33% at 8 years. Comparisons between historic controls of patients treated on other RTOG studies with standard fractionation irradiation revealed equivalent rates of pelvic tumor control, grades 3 and 4 toxicities, and survival at 3, 5 and 8 years. Conclusion: The results of this investigation suggest that, combined with brachytherapy, hyperfractionated irradiation to total parametrial doses that are about 10% above doses administered with standard fractionation pelvic irradiation was tolerated and at least as effective as standard fractionation pelvic irradiation. Further studies with higher doses of hyperfractionated irradiation, concurrent chemotherapy, and possibly extended field irradiation are indicated.

Radiation therapy and concomitant paclitaxel/carboplatin chemotherapy for muscle invasive transitional cell carcinoma of the bladder: A welltolerated combination

This review evaluates tolerance and disease control for eight patients with muscle invasive bladder cancer treated with pelvic radiotherapy and concomitant paclitaxel/carboplatin chemotherapy. From October 1996 through February 1998, eight patients were treated with pelvic radiotherapy and concomitant paclitaxel/carboplatin chemotherapy. All received from 39.60–41.40 Gy to the pelvis followed by a boost to the initial site of disease. Final tumor doses ranged from 64.80–68.40 Gy. Most patients received paclitaxel at 150 mg/m2 and carboplatin at an area under the curve (AUC) of 7 at 3-week cycles during the radiation therapy. No patient required treatment interruption. With a median follow-up of 27 months, three patients remain free of local and distant disease at follow-up intervals of 24, 25, and 31 months. No surviving locally controlled patient demonstrated late urinary or gastrointestinal morbidity. All patients with a visibly complete transurethral resection of bladder tumor (TURBT) prior to radiotherapy achieved local disease control. For this group of patients, the absolute 2-year pelvic tumor control rate is 57%. The 2-year disease-specific survival is 43%. Paclitaxel/carboplatin chemotherapy can be delivered with continuous course pelvic radiation therapy without severe acute or apparent late toxicity. This combination also appears to be effective in achieving disease control in the urinary bladder, particularly in those patients who have undergone a thorough TURBT. The authors believe that it would be reasonable to investigate this combination in future bladder conservation protocols. The combination of paclitaxel and carboplatin with radiotherapy may be of particular value in elderly patients or those with renal impairment. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 281–286 (2000). © 2000 Wiley-Liss, Inc.

Radiation therapy and concomitant paclitaxel/carboplatin chemotherapy for muscle invasive transitional cell carcinoma of the bladder:A well-tolerated combination

This review evaluates tolerance and disease control for eight patients with muscle invasive bladder cancer treated with pelvic radiotherapy and concomitant paclitaxel/carboplatin chemotherapy. From October 1996 through February 1998, eight patients were treated with pelvic radiotherapy and concomitant paclitaxel/carboplatin chemotherapy. All received from 39.60-41.40 Gy to the pelvis followed by a boost to the initial site of disease. Final tumor doses ranged from 64.80-68.40 Gy. Most patients received paclitaxel at 150 mg/m2 and carboplatin at an area under the curve (AUC) of 7 at 3-week cycles during the radiation therapy. No patient required treatment interruption. With a median follow-up of 27 months, three patients remain free of local and distant disease at follow-up intervals of 24, 25, and 31 months. No surviving locally controlled patient demonstrated late urinary or gastrointestinal morbidity. All patients with a visibly complete transurethral resection of bladder tumor (TURBT) prior to radiotherapy achieved local disease control. For this group of patients, the absolute 2-year pelvic tumor control rate is 57%. The 2-year disease-specific survival is 43%. Paclitaxel/carboplatin chemotherapy can be delivered with continuous course pelvic radiation therapy without severe acute or apparent late toxicity. This combination also appears to be effective in achieving disease control in the urinary bladder, particularly in those patients who have undergone a thorough TURBT. The authors believe that it would be reasonable to investigate this combination in future bladder conservation protocols. The combination of paclitaxel and carboplatin with radiotherapy may be of particular value in elderly patients or those with renal impairment.

Radiation therapy morbidity in carcinoma of the uterine cervix: dosimetric and clinical correlation

Purpose: To quantitate the impact of total doses of irradiation, dose rate, and ratio of doses to bladder or rectum and point A on sequelae in patients treated with irradiation alone for cervical cancer. Methods and Materials: Records were reviewed of 1456 patients (Stages IB–IVA) treated with external-beam irradiation plus two low-dose rate intracavitary insertions to deliver 70 to 90 Gy to point A. Follow-up was obtained in 98% of patients (median, 11 years; minimum, 3 years; maximum, 30 years). The relationships among various dosimetry parameters and Grade 2 or 3 sequelae were analyzed. Results: In Stage IB, the frequency of patients developing Grade 2 morbidity was 9%, and Grade 3 morbidity, 5%; in Stages IIA, IIB, III, and IVA, Grade 2 morbidity was 10% to 12% and Grade 3 was 10%. The most frequent Grade 2 sequelae were cystitis and proctitis (0.7% to 3%). The most common Grade 3 sequelae were vesicovaginal fistula (0.6% to 2% in patients with Stage I–III tumors), rectovaginal fistula (0.8% to 3%), and intestinal obstruction (0.8% to 4%). In the bladder, doses below 80 Gy correlated with less than 3% incidence of morbidity and 5% with higher doses ( p = 0.31). In the rectosigmoid, the incidence of significant morbidity was less than 4% with doses below 75 Gy and increased to 9% with higher doses. For the small intestine, the incidence of morbidity was less than 1% with 50 Gy or less, 2% with 50 to 60 Gy, and 5% with higher doses to the lateral pelvic wall ( p = 0.04). When the ratio of dose to the bladder or rectum in relation to point A was 0.8 or less, the incidence of rectal morbidity was 2.5% (8 of 320) vs. 7.3% (80 of 1095) with higher ratios ( p ≤ 0.01); bladder morbidity was 2.3% (7 of 305) and 5.8% (64 of 1110), respectively ( p = 0.02). The incidence of Grade 2 and 3 bladder morbidity was 2.9% (10 of 336) when the dose rate was less than 0.80 Gy/h, in contrast to 6.1% (62 of 1010) with higher dose rates ( p = 0.07). Rectal morbidity was 2% to 5% in Stage IB, regardless of dose rate to the rectum; in Stages IIA–B and III, morbidity was 5.2% (28 of 539) with a dose rate of 0.80 Gy or less and 10.7% (37 of 347) with higher dose rates ( p < 0.01). Multivariate analysis showed that dose to the rectal point was the only factor influencing rectosigmoid sequelae, and dose to the bladder point affected bladder morbidity. Conclusions: Various dosimetric parameters correlate closely with the incidence of significant morbidity in patients treated with definitive irradiation for carcinoma of the uterine cervix. Careful dosimetry and special attention to related factors will reduce morbidity to the lowest possible level without compromising pelvic tumor control.

Rapid growth of microscopic rectal cancer as a determinant of response to preoperative radiation therapy

Purpose: To quantify the dose-time fractionation factors in preoperative radiation therapy for microscopic pelvic deposits of rectal cancer. This provides a biologic basis for understanding and improving the results of adjuvant therapies for this disease.Methods: The reduction in incidence of pelvic relapses as a function of radiation dose and overall treatment time was determined from the literature. The displacement of dose-response curves to higher doses reflects the growth during radiation treatment of subclinical pelvic deposits which are beyond the future surgical margins.Results: Dose-response curves are steep if the effect of overall duration of radiation therapy is accounted for. The time-related displacement of these steep dose-response curves is consistent with a median doubling time for malignant clonogenic cells of about 4 or 5 days, much faster than the growth rate of the average primary tumor at diagnosis. This rapid growth is evident within the first few days of irradiation, implying that the natural growth rate of these microscopic deposits if fast, and/or that an acceleration of growth follows initiation of radiation injury with a very short lag time.Conclusion: Subclinical pelvic deposits of rectal cancer grow rapidly during preoperative radiation therapy with an adverse influence on the rate of pelvic tumor control from protracting the duration of adjuvant treatment. Low doses only offer clinically relevant reduction in risk of pelvic relapses if the overall radiation treatment time is short. For a given overall treatment duration there is a relatively steep dose-response curve, predicting that significant improvements in tumor control are possible.

Tumor Size, Irradiation Dose, and Long-Term Outcome of Carcinoma of Uterine Cervix

Purpose: To assess the impact of tumor size and extent, and dose of irradiation on pelvic tumor control, incidence of distant metastases, and disease-free survival in carcinoma of the uterine cervix. Methods and Materials: Records were reviewed of 1499 patients (Stages IA–IVA) treated with definitive irradiation (combination of external beam plus two intracavitary insertions to deliver doses of 65–95 Gy to point A, depending on stage and tumor volume). Follow-up was obtained in 98% of patients (median 11 years, minimum 3 years, maximum 30 years). The relationship between outcome and tumor size was analyzed in each stage. Pelvic tumor control was correlated with total doses to point A and to the lateral pelvic wall. Results: The 10-year actuarial pelvic failure rate in Stage IB was 5% for tumors <2 cm, 15% for 2.1–5 cm, and 35% for tumors >5 cm ( p = 0.01); in Stage IIA, the rates were 0%, 28%, and 25%, respectively ( p = 0.12). Stage IIB unilateral or bilateral nonbulky tumors <5 cm had a 23% pelvic failure rate compared with 34% for unilateral or bilateral bulky tumors >5 cm ( p = 0.13). In Stage IIB, pelvic failures were 18% with medial parametrial involvement only, compared with 28% when tumor extended into the lateral parametrium ( p = 0.05). In Stage III, unilateral parametrial involvement was associated with a 32% pelvic failure rate versus 50% for bilateral extension ( p < 0.01). Ten-year disease-free survival rates were 90% for IB tumors <2 cm, 76% for 2.1–4 cm, 61% for 4.1–5 cm, and 47% for >5 cm ( p = 0.01); in Stage IIA, the rates were 93%, 63%, 39%, and 59%, respectively ( p ≤ 0.01). Patients with Stage IIB medial parametrial involvement had better 10-year disease-free survival (67%) than those with lateral parametrial extension (56%) ( p = 0.02). Stage III patients with unilateral tumor extension had a 48% 10-year disease-free survival rate compared with 32% for bilateral parametrial involvement ( p ≤ 0.01). The presence of endometrial extension or tumor only in the endometrial curettings had no significant impact on pelvic failure. However, in patients with Stage IB disease, the incidence of distant metastases was 31% with positive curettings, 15% with negative curettings, and 22% with admixture ( p ≤ 0.01). In Stage IIA, the corresponding values were 51%, 33%, and 18% ( p = 0.05). The 10-year disease-free survival rates in Stage IB were 67% with positive curettings, 81% for negative curettings, and 77% for admixture ( p = 0.02); in Stage IIA, the rates were 45%, 66%, and 67%, respectively ( p = 0.14). Because this is not a prospective Phase II dose-escalation study, the correlation of doses of irradiation with pelvic tumor control in the various stages and tumor size groups is not consistent. Nevertheless, with Stage IB and IIA tumors <2 cm in diameter, the pelvic failure rate was under 10% with doses of 70–80 Gy to point A, whereas for larger lesions even doses of 85–90 Gy resulted in 25% to 37% pelvic failure rates. In Stage IIB with doses of 70 Gy to point A, the pelvic failure rate was about 50% compared with about 20% in nonbulky and 30% in bulky tumors with doses >80 Gy. In Stage III unilateral lesions, the pelvic failure rate was about 50% with ≤70 Gy to point A versus 35% with higher doses, and in bilateral or bulky tumors it was 60% with doses <70 Gy and 50% with higher doses. Conclusions: Clinical stage and size of tumor are critical factors in prognosis, therapy efficacy, and evaluation of results in carcinoma of the uterine cervix. The doses to point A suggest that for lesions <2 cm, doses of 75 Gy result in ≤10% pelvic failures, whereas in more extensive lesions, even with doses of 85 Gy, the pelvic failure rate is about 30%; and in Stage IIB–III tumors, doses of 85 Gy result in 35–50% pelvic failures. Refinements in brachytherapy techniques and/or use of agents to selectively sensitize the tumors to irradiation will be necessary to improve the present results in invasive carcinoma of the uterine cervix.