Rectal dose-volume constraints in high-dose radiotherapy of localized prostate cancer

PURPOSE: To investigate the relationship between rectal bleeding and dosimetric-clinical parameters in patients receiving three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. METHODS: In a retrospective national study (AIROPROS01-01, AIRO: Associazione Italiana Radioterapia Oncologica), planning/clinical data for 245 consecutive patients with stage T1-4N0-x prostate carcinoma who underwent 3D-CRT to 70-78 Gy (ICRU point) were pooled from four Italian institutions. The correlation between late rectal bleeding and rectal dose-volume data (the percentage of rectum receiving more than 50, 55, 60, 65, 70, and 75 Gy [V(50-70)]) and other dosimetric and clinical parameters were investigated in univariate (log-rank) and multivariate (Cox regression model) analyses. Median follow-up was 2 years. RESULTS: Twenty-three patients were scored as late bleeders according to a modified RTOG definition (Grade 2: 16; Grade 3: 7); the actuarial 2-year rate was 9.2%. Excepting V75, all median and third quartile V(50-70) values were found to be significantly correlated with late bleeding at univariate analysis. The smallest p value was seen for V(50) below/above the third quartile value (66%). The V70 (cut-off value: 30%) was found to be also predictive for late bleeding. In the high-dose subgroup (74-78 Gy), Grade 3 bleeding was highly correlated with this constraint. The predictive value of both V(50) and V(70) was confirmed by multivariate analyses. CONCLUSIONS: The present article provides evidence for correlation between rectal DVH parameters and late rectal bleeding in patients treated with curative intent with 3D-CRT. To keep the rate of moderate/severe rectal bleeding below 5-10%, it seems advisable to limit V(50) to 60-65%, V(60) to 45-50%, and V70 to 25-30%.     

Rectal cancer: The radiation basis of radiotherapy, target volume

Since the implementation of preoperative chemoradiotherapy and mesorectal excision, the 5-year rates of locoregional failures in T3-T4 N0-N1 M0 rectal cancer fell from 25-30% thirty years ago to 5-8% nowadays. A critical analysis of the locoregional failures sites and mechanisms, as well as the identification of nodal extension, helps the radiation oncologist to optimize the radiotherapy target definition. The upper limit of the clinical target volume is usually set at the top of the third sacral vertebra. The lateral pelvic nodes should be included when the tumor is located in the distal part of the rectum. The anal sphincter and the levator muscles should be spared when a conservative surgery is planned. In case of abdominoperineal excision, the ischiorectal fossa and the sphincters should be included in the clinical target volume. A confrontation with radiologist and surgeon is mandatory to improve the definition of the target volumes to be treated.     

Rectal cancer staging

Endorectal-US is the most suitable imaging technique in the initial staging of rectal cancer and it is mostly accurate in evaluating early stages and in demonstrating the perirectal spread of cancer tissue. CT is not able to demonstrate the layers of the rectal wall and its accuracy in demonstrating the invasion of muscolaris propria and perirectal fat is lower than other techniques, so its use in local staging is not recommended. MRI is mostly accurate in evaluating the mesorectum and the mesorectal fascia which are considered the most relevant prognostic factors for local recurrence. Lymph node evaluation is a challenge for every imaging techniques since lymph node size is not a reliable criterion for diagnosing metastatic involvement. Nuclear medicine has a remarkable role in the work-up of rectal cancer and in the next future the combination of FDG PET in conjunction with a dedicated contrast enhanced CT protocols could become a single-step staging procedure.     

Rectal sequelae after conformal radiotherapy of prostate cancer: dose-volume histograms as predictive factors.

PURPOSE: To identify clinically relevant parameters predictive of late rectal bleeding derived from cumulative dose-volume histograms (DVHs) of the rectum after conformal radiotherapy of prostate cancer. MATERIALS AND METHODS: One hundred and nine patients treated with 3D conformal radiotherapy between 1/1994 and 1/1996 for localized prostate cancer (clinical stage T1-T3) were available for analysis. All patients received a total dose of 66 Gy/2 Gy per fraction (specified at the International Commission on Radiation Units and Measurements ICRU reference point). DVHs of the contoured rectum were analyzed by defining the absolute (aV) and relative (rV) rectum volume that received more than 30% (V30), 50% (V50), 70% (V70), 80% (V80), 90% (V90) and 100% (V100) of the prescribed dose. Additionally, a new aspect of DVH analysis was investigated by calculation of the area under the DVH-curve between several dose levels (area under the curve (AUC)-DVH). DVH-variables were correlated with radiation side effects evaluated in 3-6 months intervals and graded according to the EORTC/RTOG score. The median follow-up was 30 months (12-60 months). RESULTS: Univariate and multivariate stepwise Cox-Regression analysis including age, PTV, rectum size, rV100, rV90, rV80, rV70, rV50 rV30 and aV30 to aV100 were calculated. Late rectal bleeding (EORTC/RTOG grade 2) was significantly correlated with the percentage of rectum volume receiving > or = 90% of the prescribed dose (rV90) (P = 0.007) and inversely correlated in a significant way with the size of contoured rectum (P = 0.006) in multivariate analysis. In our series, a proportion of the rectum volume > or = 57% were included in the 90%-isodose (rV90 > or = 57%) in one half of the patients, with an actuarial incidence of 31% of late rectal bleeding at 3 years. In the other half of the patients, when rV90 < 57%, the 3-year actuarial incidence was 11% (P < 0.03). CONCLUSION: Our data demonstrate a dose-volume relationship at the reference dose of 60 Gy ( approximately 90% of the prescribed dose) with respect to late rectal toxicity. The rV90 seems to be the most useful and easily obtained parameter when comparing treatment plans to evaluate the risk of rectal morbidity.     

Cost-effectiveness of preoperative radiotherapy in rectal cancer: results from the Swedish Rectal Cancer Trial

PURPOSE: The Swedish Rectal Cancer Trial (SRCT) demonstrated that a short-term regimen of high-dose fractionated preoperative radiotherapy (5 x 5 Gy) reduced the local recurrence rates and improved overall survival. This has had an impact on the primary treatment of rectal cancer. The current study investigated the cost-effectiveness of the new combined approach. METHODS AND MATERIALS: After an 8-year follow-up, in-hospital and outpatient costs related to the treatment of rectal cancer and its complications were analyzed for 98 randomly allocated patients who participated in the SRCT from a single Swedish health care region. The costs were then related to the clinical data from the SRCT regarding complications, local and distant recurrences, and survival. RESULTS: The total cost for a nonirradiated patient was US$30,080 compared with US$35,268 for an irradiated patient. The surgery-alone group had increased costs related to local recurrences, and the radiotherapy group had increased costs for irradiation and complications. With a survival benefit of 21 months (retrieved from the SRCT), the cost for a saved year was US$3654. Sensitivity analyses for different rates of local recurrences, the costs related to complications and less marked survival benefit showed that this figure could vary up to US$15,228. CONCLUSION: The cost for a life-year saved in these data was US$3654. This figure could reach US$15,228 in the most pessimistic setting of the sensitivity tests, a cost still comparable with other well-accepted medical interventions.     

Rectal dose reduction with IMRT for prostate radiotherapy

Dose escalation in radiation therapy has led to increased control rates with some clinical trial evidence that rectal toxicity may be reduced when using intensity-modulated radiotherapy (IMRT) over 3D conformal radiotherapy (3DCRT) for dose-escalated prostate radiotherapy. However, IMRT for prostate patients is not yet standard in many Australian radiation oncology centres. This study investigates dosimetric changes that can be observed between IMRT and 3DCRT in prostate radiotherapy. Fifteen patients were selected for analysis. Two target definitions were investigated – prostate-only and prostate plus seminal vesicles (p + SVs). A five-field 3DCRT and seven-field IMRT plan were created for each patient and target definition. The planning target volume coverage was matched for both plans. Doses to the rectum, bladder and femoral heads were compared using dose volume histograms. The rectal normal tissue complication probabilities (NTCPs) were calculated and compared for the 3DCRT and IMRT plans. The delivery efficiency was investigated. The IMRT plans resulted in reductions in the V25, V50, V60, V70 and V75 Gy values for both the prostate-only and p + SVs targets. Rectal NTCP was reduced with IMRT for three different sets of model parameters. The reductions in rectal dose and NTCP were much larger for the p + SVs target. Delivery of IMRT plans was less efficient than for 3DCRT plans. IMRT resulted in superior plans based on dosimetric and biological endpoints. The dosimetric gains with IMRT were greater for the more complex p + SVs target. The gains made came at the cost of decreased delivery efficiency.     

Rectal dose-volume differences using proton radiotherapy and a rectal balloon or water alone for the treatment of prostate cancer

PURPOSE: To describe dose-volume values with the use of water alone vs. a rectal balloon (RB) for the treatment of prostate cancer with proton therapy. MATERIALS AND METHODS: We analyzed 30 proton plans for 15 patients who underwent CT and MRI scans with an RB or water alone. Simulation was performed with a modified MRI endorectal coil and an RB with 100 mL of water or water alone. Doses of 78-82 gray equivalents were prescribed to the planning target volume. The two groups were compared for three structures: rectum, rectal wall (RW), and rectal wall 7 cm (RW7) at the level of the planning target volume. RESULTS: Rectum and RW volumes radiated to low, intermediate, and high doses were small: rectum V10, 33.7%; V50, 17.3%; and V70, 10.2%; RW V10, 32.4%; V50, 20.4%; and V70, 14.6%. The RB effectively increased the rectal volume for all cases (139.8 +/- 44.9 mL vs. 217.7 +/- 32.2 mL (p < 0.001). The RB also decreased the volume of the rectum radiated to doses V10-V65 (p < or = 0.05); RW for V10-V50; and RW7 for V10-V35. An absolute rectum V50 improvement >5% was seen for the RB in 5 of 15 cases, for a benefit of 9.2% +/- 2.3% compared with 2.4% +/- 1.3% for the remaining 10 cases (p < 0.001). Similar benefit was seen for the rectal wall. No benefit was seen for doses > or =70 gray equivalents for the rectum, RW, or RW7. No benefit of < or =1% was seen with an RB in 46% for the rectum V70 and in 40% for the rectal wall V70. CONCLUSIONS: Rectum and rectal wall doses with proton radiation were low whether using water or an RB. Selected patients will have a small but significant advantage with an RB; however, water alone was well tolerated and will be an alternative for most patients.     

Rectal and bladder motion during conformal radiotherapy after radical prostatectomy.

BACKGROUND AND PURPOSE: To investigate the extent and the impact of rectum and bladder motion during adjuvant conformal radiotherapy (3DCRT) after radical prostatectomy (RP). MATERIALS AND METHODS: Nine patients previously operated with RP and treated with early adjuvant 3DCRT were considered for this investigation. Weekly CT scans were collected during treatment (CT1-CTn, n=4-6) and were 3D matched using bony anatomy with the planning CT (CT0). A single observer drew the contours of rectum and bladder on all CTs. The CTV (prostate+/-seminal vesicles surgical bed) was contoured on CT0 by a single observer and a 4-field 3DCRT technique was planned: dose statistics/dose-volume histograms (DVH) of the rectum and bladder were calculated for each contour referred to CT0, CT1...CTn. Average DVHs during the treatment were then calculated and compared with the planned DVH. Cranial, caudal, anterior and posterior shifts of rectum and bladder were also assessed by lateral BEV projections. NTCP values for the rectum were also calculated using the Lyman-Kutcher model. RESULTS: Random variations of volume and DVHs due to variable filling content were found for the bladder; a trend of the bladder to be more empty during therapy with respect to CT0 was also found (median values: 45 cm3 vs. 79 cm3, P=0.02). Regarding the rectum, 6/9 patients showed an average DVH 'worse' than the planned one (up to 10-20%). BEV and volume analyses showed that the rectal volume decreased in 3/9 patients after the first week. In 6/9 patients a systematic anterior shift of the cranial half of the rectum was detected and found to be correlated with a corresponding shift of the posterior border of CTV contoured by five different observers. The average rectal NTCP during therapy was systematically higher than the NTCP referred to CT0 (average increase 1.2%; range 0.0-3.7%, for a 70 Gy ICRU dose, P=0.01). CONCLUSIONS: The impact of systematic uncertainty due to rectal wall motion seems to be relatively high for patients treated with adjuvant 3DCRT after RP. The detected trend of the rectum in migrating anteriorly during therapy is consistent with post-surgery settlement effects and/or some modification of rectum mobility due to irradiation. Rectal motion (and consequent shifts of CTV) was large at the half cranial portion of the rectum while it was very small below the flexure.     

Rectal cancer Information dedicated to cancer patients and relatives

In response to the evolution of the information-seeking behaviour of patients and concerns from health professionals regarding cancer patient information, the French National Federation of Comprehensive Cancer Centres (FNCLCC) introduced, in 1998, an information and education program dedicated to patients and relatives, the SOR SAVOIR PATIENT program. The methodology of this program adheres to established quality criteria regarding the elaboration of patient information. Cancer patient information, developed in this program, is based on clinical practice guidelines produced by the FNCLCC and the twenty French regional cancer centres, the National League against Cancer, The National Cancer Institute, the French Hospital Federation, the National Oncology Federation of Regional and University Hospitals, the French Oncology Federation of General Hospitals, many learned societies, as well as an active participation of patients, former patients and caregivers. The handbook SOR SAVOIR PATIENT Understanding rectal cancer is an adapted version of the clinical practice guidelines (CPG) Standards, Options and Recommendations for rectal cancer. It is meant to provide a basis for the explanation of the disease and treatments and to facilitate discussions with the healthcare team. It is available from the FNCLCC (101, rue de Tolbiac, 75013 Paris, Tel. (0033) 1 44 23 04 68, www.fnclcc.fr). This document has been validated at the end of 2004 and published in 2005. SOR SAVOIR PATIENT guides are systematically updated when new research becomes available. Information leaflets, extracted from the handbook SOR SAVOIR PATIENT Understanding rectal cancer and published in this edition of the Bulletin du cancer, allow patients to better understand colonoscopy and colostomy, which represent an important patient information need. These articles are meant to inform patients and relatives about the disease and its treatments. It also offers health professionals a synthetic evidence-based patient information source which facilitates discussions with the patient.     

Rectal cancer surgery: A brief history

In the last 250 years, the treatment of rectal cancer has changed dramatically. Once considered an incurable disease, combined modality therapy has improved mortality from 100% to less than 4% for locally advanced rectal cancer. This dramatic reduction paralleled surgical techniques based on a growing understanding of anatomy and disease pathology. In order to understand modern treatment, it is necessary to recognize the achievements of preceding surgeons.     

Rectal bleeding, fecal incontinence, and high stool frequency after conformal radiotherapy for prostate cancer: normal tissue complication probability modeling

PURPOSE: To analyze whether inclusion of predisposing clinical features in the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model improves the estimation of late gastrointestinal toxicity. METHODS AND MATERIALS: This study includes 468 prostate cancer patients participating in a randomized trial comparing 68 with 78 Gy. We fitted the probability of developing late toxicity within 3 years (rectal bleeding, high stool frequency, and fecal incontinence) with the original, and a modified LKB model, in which a clinical feature (e.g., history of abdominal surgery) was taken into account by fitting subset specific TD50s. The ratio of these TD50s is the dose-modifying factor for that clinical feature. Dose distributions of anorectal (bleeding and frequency) and anal wall (fecal incontinence) were used. RESULTS: The modified LKB model gave significantly better fits than the original LKB model. Patients with a history of abdominal surgery had a lower tolerance to radiation than did patients without previous surgery, with a dose-modifying factor of 1.1 for bleeding and of 2.5 for fecal incontinence. The dose-response curve for bleeding was approximately two times steeper than that for frequency and three times steeper than that for fecal incontinence. CONCLUSIONS: Inclusion of predisposing clinical features significantly improved the estimation of the NTCP. For patients with a history of abdominal surgery, more severe dose constraints should therefore be used during treatment plan optimization.     

Rectal cancer therapy compatible with preservation of function

Rectal cancer surgery causes often postoperative morbidities such as defecation disturbance, dysuria and male sexual impotence. Compatibility of cancer eradication and function preservation are the problem should be resolved in the rectal cancer surgery. Defecation function were preserved in the patients with middle and upper rectal cancer by anterior resection transsacral resection, invagination or pull-through operation. Since 1984, usage of suture instruments made it practicable to increase sphincter preserving operation up to more than 65% of rectal cancer. Postoperative 5-years survivals were 81% of anterior resection, 71% of invagination operation and 57% of pull-through. Autonomic nerves preserving operation (ANP), aimed to prevent the urinary and sexual disfunction were studied both sides of the cancer spreads and extend of nerve plexuses. And ANP were adopted to the 185 cancers, limited to the submucosa or the proper muscle coat, by Study Group of Welfare Ministry. Their postoperative disfunction decreased to 15% of urination and 21% of male potency, while 33% and 81% respectively following conventional operation. Local excision for early cancer, which are defined as mucosal or submucosal cancer are discussed.