Acute Bowel Toxicity Research Articles

Should Preoperative or Postoperative Therapy Be Administered in the Management of Rectal Cancer?

Combined-modality therapy consisting of surgery, radiation, and chemotherapy with 5-fluorouracil is the recommended management for patients with stage II and III rectal cancer. The place of radiation therapy as part of this combined modality treatment for localized rectal cancer will be reviewed, and some of the novel chemoradiation combinations under investigation will be highlighted. Currently, there are two sequencing approaches for the adjuvant administration of pelvic radiation therapy. The first is surgical resection and, if the tumor is stage T(3-4) and/or N(1-2), adjuvant postoperative chemoradiation and further chemotherapy. The second approach for patients with ultrasound T(3-4) or clinical T(4) disease is preoperative therapy followed by surgical resection and postoperative chemotherapy. The adjuvant radiation management approach in the United States and Europe has been shifting toward preoperative therapy to promote sphincter-preserving surgery and decrease acute and late bowel toxicity. The recently published 5-year results of the randomized German CAO/ARO/AIO 94 trial of preoperative versus postoperative chemoradiation support a standard preoperative treatment approach. Preoperative chemoradiation therapy also allows for the investigation of innovative agents (capecitabine, oxaliplatin, irinotecan, bevacizumab, and cetuximab) in combination with pelvic radiation. These new combinations may have the potential to further increase the therapeutic benefit of neoadjuvant therapy.

Acute small bowel toxicity and preoperative chemoradiotherapy for rectal cancer: Investigating dose–volume relationships and role for inverse planning

The relationship between volume of irradiated small bowel (VSB) and acute toxicity in rectal cancer radiotherapy is poorly quantified, particularly in patients receiving concurrent preoperative chemoradiotherapy. Using treatment planning data, we studied a series of such patients. Details of 41 patients with locally advanced rectal cancer were reviewed. All received 45 Gy in 25 fractions over 5 weeks, 3-4 fields three-dimensional conformal radiotherapy with daily 5-fluorouracil and folinic acid during Weeks 1 and 5. Toxicity was assessed prospectively in a weekly clinic. Using computed tomography planning software, the VSB was determined at 5 Gy dose intervals (V5, V10, etc.). Eight patients with maximal VSB had dosimetry and radiobiological modeling outcomes compared between inverse and conformal three-dimensional planning. VSB correlated strongly with diarrheal severity at every dose level (p<0.03), with strongest correlation at lowest doses. Median VSB differed significantly between patients experiencing Grade 0-1 and Grade 2-4 diarrhea (p<or=0.05). No correlation was found with anorexia, nausea, vomiting, abdominal cramps, age, body mass index, sex, tumor position, or number of fields. Analysis of 8 patients showed that inverse planning reduced median dose to small bowel by 5.1 Gy (p=0.008) and calculated late normal tissue complication probability (NTCP) by 67% (p=0.016). We constructed a model using mathematical analysis to predict for acute diarrhea occurring at V5 and V15. A strong dose-volume relationship exists between VSB and acute diarrhea at all dose levels during preoperative chemoradiotherapy. Our constructed model may be useful in predicting toxicity, and this has been derived without the confounding influence of surgical excision on bowel function. Inverse planning can reduce calculated dose to small bowel and late NTCP, and its clinical role warrants further investigation.

Dose / Volume Relationships and Acute Small Bowel Toxicity in Patients Undergoing Pre-operative Chemoradiation (PRE-OP CRT) for Locally Advanced Rectal Cancer (LARC)

Dose / Volume Relationships and Acute Small Bowel Toxicity in Patients Undergoing Pre-operative Chemoradiation (PRE-OP CRT) for Locally Advanced Rectal Cancer (LARC)

Confirmation of the Dose-Volume Relationship for Acute Small Bowel Toxicity During the Treatment of Rectal Cancer

Confirmation of the Dose-Volume Relationship for Acute Small Bowel Toxicity During the Treatment of Rectal Cancer

Comparing measures of acute bowel toxicity in patients with prostate cancer treated with external beam radiation therapy

This study strives to compare early measures of bowel toxicity in patients with prostate cancer receiving definitive or adjuvant 3D conformal external beam radiation therapy and concurrent daily endorectal application of amifostine. Eighteen patients were enrolled in the clinical study with a median follow-up of 12 months. Prescription doses ranged from 66 Gy to 76 Gy with a daily fractionation of 2 Gy. Acute bowel toxicity was measured at baseline, at Weeks 5 and 7 of radiotherapy, and at 1 and 3 months after the completion of therapy. Measures of acute bowel toxicity included the Radiation Therapy Oncology Group (RTOG) acute radiation morbidity scoring criteria, Expanded Prostate Cancer Index Composite (EPIC) self-assessment questionnaires, and proctoscopic examinations. The mean EPIC bowel scores changed significantly through the course of therapy and follow-up (p < 0.0001), with a progressive decrease in scores at Weeks 5 and 7 of treatment, a partial recovery at 3 months, and a correlation to the gold standard RTOG grade (p = 0.004). Proctoscopic toxicity scores were low, did not vary over time, and did not correlate with either EPIC or RTOG scores. The EPIC questionnaire measurements are most sensitive to changes in acute bowel toxicity through a course of radiotherapy and correlate with RTOG acute toxicity scores. Endoscopic examination of the rectal mucosa at the end and immediate follow-up of a course of therapy does not seem to be informative or reproducible between observers in the acute setting.

Do Serum Levels of Eosinophil Granule-derived Protein Change in Patients Undergoing Pelvic Radiotherapy?

Eosinophils have an important role in the pathogenesis of inflammatory bowel disease, with faecal levels of the eosinophil granule proteins, eosinophil cationic protein (ECP) and eosinophil protein X (EPX) reflecting disease activity. Eosinophil crypt abscesses are a characteristic histological finding in acute gastrointestinal radiation-induced mucosal damage. This pilot study aimed to investigate changes in serum levels of ECP/EPX during pelvic radiotherapy. Patients with no history of inflammatory bowel disease, starting a 5-week course of pelvic radiotherapy, had serum ECP/EPX levels measured before radiotherapy and during the fourth week of treatment. Bowel toxicity was graded at week 4 using the Common Toxicity Criteria Scale. Fifteen patients who were to undergo adjuvant radiotherapy for gynaecological cancer were recruited. The mean serum levels of ECP and EPX before treatment were 17.3 microg/l (range 2.0-49.3 microg/l) and 37.3 microg/l (range 12.0-94.0 microg/l), respectively. The mean serum levels during week 4 of radiotherapy for ECP and EPX were 43.0 microg/l (range 2.4-164.0 microg/l) and 38.7 microg/l (range 9.0-79.0 microg/l), respectively. Serum ECP levels increased at week 4 compared with levels before radiotherapy (P = 0.02). Acute bowel toxicity was seen in 12 patients (80%) at week 4: Grade 1 in 25% patients and Grade 2 in 75%. In this small study, no correlation was seen between acute bowel toxicity at week 4 and serum ECP or EPX levels. Serum ECP levels increase in response to pelvic irradiation. This may reflect the known involvement of eosinophils in the acute response to radiotherapy. Further study is required to determine when levels start to rise and their relationship to the degree of acute bowel toxicity.

Topical phenylephrine in the treatment of radiation-induced faecal incontinence

Acute bowel toxicity after pelvic radiotherapy is defined as occurring within 3 months of the start of treatment; chronic gastrointestinal toxicity may continue after the acute phase or start after a latent period. One in five patients develop chronic faecal incontinence affecting quality of life; how best to treat these patients is not known. This retrospective study aimed to determine the effects of a new agent, phenylephrine gel, in the treatment of chronic radiation-induced faecal incontinence. Patients prescribed phenylephrine gel for new-onset faecal incontinence after radiotherapy were identified from our database of patients treated in a specialist radiation-induced bowel damage clinic since 2000. Changes in the level of faecal incontinence were assessed using the Vaizey faecal incontinence scoring system before and after treatment. Fifteen patients (nine men and six women) of mean age 70.5 years (standard deviation 8.2, age range 56-82 years) were treated with phenylephrine gel a median of 43 months after completing radiotherapy. The median Vaizey score before treatment with phenylephrine gel was 17 (interquartile range [IQR] 14-20) and after treatment was 14 (IQR 11-18) (P = 0.005). The median length of treatment with phenylephrine gel was 28 days (IQR 28-365). Scores improved in 11 out of 15 patients; four out of 15 patients showed substantial improvements of 7 or more points; and seven patients considered the gel helpful. Topical phenylephrine gel for the treatment of radiation-induced faecal incontinence has not been previously reported. This small, retrospective study suggests that it may help most patients and, in some, the improvement may be substantial. However, larger placebo-controlled prospective studies are required.

Treatment with a belly-board device significantly reduces the volume of small bowel irradiated and results in low acute toxicity in adjuvant radiotherapy for gynecologic cancer: results of a prospective study

Background and purpose To determine whether treatment prone on a belly-board significantly reduces the volume of small bowel irradiated in women receiving adjuvant radiotherapy for gynecologic cancer, and to prospectively study acute small bowel toxicity using an accepted recording instrument. Material and methods Thirty-two gynecologic patients underwent simulation with CT scanning supine and prone. Small bowel was delineated on every CT slice, and treatment was prone on the belly-board using 3–5 fields—typically Anterior, Right and Left Lateral, plus or minus Lateral Boosts. Median prescribed dose was 50.4 Gy and all treatments were delivered in 1.8 Gy fractions. Concomitant Cisplatin was administered in 13 patients with cervical carcinoma. Comparison of small bowel dose–volumes was made between supine and prone, with each subject acting as their own matched pair. Acute small bowel toxicity was prospectively measured using the Common Toxicity Criteria: Version 2.0. Results Treatment prone on the belly-board significantly reduced the volume of small bowel receiving ≥100; ≥95; ≥90; and ≥80% of the prescribed dose, but not ≥50%. This was found whether volume was defined in cubic centimeters or % of total small bowel volume. Of 29 evaluable subjects, 2 (7%) experienced 1 episode each of grade 3 diarrhoea. All other toxicity events were grade 2 or less and comprised diarrhoea (59%), abdominal pain or cramping (48%), nausea (38%), anorexia (17%), vomiting (10%). There were no Grade 4 events and no treatment days were lost due to toxicity. Conclusions Treatment prone on a belly-board device results in significant small bowel sparing, during adjuvant radiotherapy for gynecologic cancer. The absence of Grade 4 events or Treatment Days Lost compares favorably with the published literature.

The stanford experience with preoperative chemoradiation using CPT-11 and 5-FU in locally advanced rectal cancer: Toxicities and outcomes

To evaluate the tolerability and efficacy of a preoperative regimen for locally advanced rectal cancer patients consisting of CPT-11 and continuous infusion 5-FU with concurrent pelvic radiotherapy. From April 1999 through August 2002, 39 evaluable patients who were clinical stage T3/T4 or node positive by endorectal ultrasound were enrolled on a phase II protocol using CPT-11 (50mg/m2) given on Days 1, 8, 15, and 22 and protracted infusion 5FU (200mg/m2 daily, 7d/wk) given throughout the radiation course, concurrent with pelvic radiotherapy (45 Gy to pelvis, 5.4 Gy boost to tumor and involved nodes). Surgical resection was performed 6–10 weeks after completion of the preoperative regimen. Some patients also received adjuvant chemotherapy of 5FU/LV or capecitabine. The regimen proved to be challenging, with 24/39 (62%) requiring a chemotherapy dose reduction or interruption and 9/39 (23%) requiring a radiation split of 3 days or more. The most significant acute grade 3 toxicity was diarrhea (16/39, or 41%). A complete pathologic response rate of 36% was observed. Another 15% showed only microscopic residual disease at surgery. Sixty-two percent (24/39) of patients underwent a sphincter-sparing surgery, 36% (14/39) underwent an APR, and 3% (1/39) underwent a pelvic exenteration. One patient required subsequent conversion to an ostomy due to surgical complications. Of the 30 surgeries completed at Stanford, 6 patients were noted to have an anastamotic leak, 3 of which resulted in fistulas; 2 patients had a pelvic abscess without evident leaks; 2 patients experienced delayed perineal wound healing or perineal abscesses; and 1 patient had an abdominal wound dehiscence. Five patients within this group required second surgeries to address these complications. At a median follow-up of 34 months, the overall survival was 79% and disease-free survival was 67%. Locoregional and distant metastases have been identified in 13%; no isolated local recurrences have been observed to date. The cause-specific mortality was 10%. Ten percent of patients are lost to follow-up. Preoperative CPT-11/continuous infusion 5-FU with concurrent pelvic radiotherapy is an extremely active regimen resulting in an excellent pathologic response. However, significant acute bowel toxicity and a concerning surgical complication rate outweighed the marginal benefit in pathologic response over that seen in less toxic regimens

890 Acute small bowel and colon toxicity after pelvic IMRT for prostate cancer

890 Acute small bowel and colon toxicity after pelvic IMRT for prostate cancer

Factors determining acute normal tissue reactions during postoperative radiotherapy in endometrial cancer: analysis of 317 consecutive cases.

Acute radiotherapy reactions are commonly underestimated and under-reported in the literature. Our aim was to evaluate the incidence and risk factors for acute reactions during postoperative radiotherapy in endometrial cancer patients. Performed was detailed retrospective analysis of 317 endometrial cancer patients given postoperative radiotherapy. Two hundred forty seven patients (78%) received both intracavitary (BRT) and external beam irradiation (EBRT), 49 patients (15%) received only BRT and 21 patients (7%) - only EBRT. BRT included radium (Ra) or cesium (Cs). The mean total dose at 0.5 cm for Ra and Cs was 50.5+/-10.3 Gy and 48.4+/-15.0 Gy, respectively, and the mean dose rate - 0.47+/-0.06 Gy/h and 1.42+/-0.41 Gy/h, respectively. Mean EBRT dose in the ICRU reference point was 49.0+/-3.7 Gy given in fractions of 1.54-2.49 Gy (mean 2.0+/-0.17 Gy). Radiotherapy and Oncology Group classification system was employed to score acute reactions. The impact of patient- and treatment-related factors on the risk of acute bowel and urinary bladder reactions was assessed with uni- and multivariate tests. Acute radiotherapy reactions of any grade occurred in 265 patients (84%) including bowel complications in 66% and urinary bladder complications in 36%. There were 21 severe (grade 3 or 4) reactions, all but one seen in the patients treated with combined EBRT and BRT. Higher total dose (P=0.024), higher EBRT dose (P=0.022) and higher age (P=0.026) were correlated with increased acute bowel toxicity in univariate analysis. Multivariate analysis showed that higher EBRT dose (P=0.015) and older age (P=0.016) were independently correlated with the risk of acute bowel events. Higher total dose (P=0.009), BRT dose (P=0.029), BRT dose rate (P=0.004), EBRT fraction size (P=0.007), the use of Cs BRT (P=0.001) and lower parity (P=0.041) were correlated with increased risk of acute bladder toxicity in univariate test. Multivariate analysis demonstrated that the independent risk factors for acute bladder events were BRT dose rate (P=0.002) and low parity (P=0.042) and there was a trend for EBRT dose (P=0.076). In multivariate analysis there was no impact of other clinical factors (FIGO stage, diabetes mellitus, hypertension, prior abdominal surgery) on the risk of acute bowel and/or bladder reactions nor was the impact of surgery-to-radiotherapy interval, overall radiotherapy time and overall treatment time. The risk of acute reactions depends both on treatment-related (BRT dose rate, EBRT dose) and patient-related factors (age, parity). Precise treatment prescription, planning and verification are of paramount concern. Further studies are warranted to evaluate the impact of extrinsic and intrinsic factors associated with acute normal tissue injury.

Relationship between acute and late normal tissue injury after postoperative radiotherapy in endometrial cancer

Purpose : To evaluate the relationship between acute and late normal tissue reactions in 317 consecutive endometrial cancer patients treated with surgery and adjuvant radiotherapy (RT). Methods : The data of 317 patients (staging according to the International Federation of Gynecology and Obstetrics) treated with postoperative RT were analyzed. Both low-dose-rate brachytherapy and external beam RT were applied in 247 patients (78%); brachytherapy only in 49 (15%) and external beam irradiation only in 21 (7%). The median follow-up was 7.3 years (range 4–21). The European Organization for Research and Treatment of Cancer, Radiation Therapy Oncology Group system with elements of the late effects of normal tissue, subjective, objective, management, analytic (LENT/SOMA) scale was used to score the RT reactions. The correlation between the occurrence and severity of acute and late bowel and bladder toxicity, as well as the relationship between the severity of acute effects and time to occurrence of late reactions, were assessed using linear and logistic regression analyses. Results : Of the 317 patients, 268 (85%) experienced acute RT reactions of any grade. Severe acute bowel reactions were observed in 15 patients (5%), urinary bladder complications in 1 patient (0.5%), cutaneous in 1 patient (0.5%), and vaginal in 1 patient (0.5%). Severe acute hematologic toxicity was seen in 3 patients (1%). A total of 158 patients (51%) experienced late RT reactions of any grade. Severe late bowel reactions were observed in 19 patients (6%), urinary bladder in 5 (2%), vaginal in 3 (1%), and bone in 10 (4%). When all toxic events were considered, there was a highly significant correlation between the acute and late bowel reactions ( p <0.001), but the acute and late urinary bladder reactions did not correlate ( p = 0.64). The grade of acute toxicity was found to predict the grade of late toxicity for the bowel but not for the bladder ( p <0.001 and p = 0.47, respectively). The severity of acute bowel and bladder toxicity did not correlate with the time to occurrence of late toxicity in these locations ( p = 0.34 and p = 0.47, respectively). Conclusion : Patients with increased acute bowel toxicity during postoperative RT for endometrial cancer have an increased risk of late bowel injury. A higher grade of acute bowel complications correlated with more severe late events, but was not predictive for its latency time. These findings suggest the possibility of an early indication of patients with an increased risk of late toxicity in whom preventive measures might be attempted.

The dose-volume realationship of acute small bowel toxicity from concurrent 5-FU-based chemotherapy and radiation therapy for rectal cancer

Purpose: A direct relationship between the volume of small bowel irradiated and the degree of acute small bowel toxicity experienced during concurrent 5-fluorouracil (5-FU)-based chemoradiotherapy for rectal carcinoma is well recognized but poorly quantified. This study uses three-dimensional treatment-planning tools to more precisely quantify this dose-volume relationship. Methods and Materials: Forty patients receiving concurrent 5-FU-based chemotherapy and pelvic irradiation for rectal carcinoma had treatment-planning CT scans with small bowel contrast. A median isocentric dose of 50.4 Gy was delivered using a posterior-anterior and opposed lateral field arrangement. Bowel exclusion techniques were routinely used, including prone treatment position on a vacuum bag cradle to allow anterior displacement of the abdominal contents and bladder distension. Individual loops of small bowel were contoured on each slice of the planning CT scan, and a small bowel dose-volume histogram was generated for the initial pelvis field receiving 45 Gy. The volume of small bowel receiving each dose between 5 and 40 Gy was recorded at 5-Gy intervals. Results: Ten patients (25%) experienced Common Toxicity Criteria Grade 3+ acute small bowel toxicity. A highly statistically significant association between the development of Grade 3+ acute small bowel toxicity and the volume of small bowel irradiated was found at each dose level. Specific dose-volume threshold levels were found, below which no Grade 3+ toxicity occurred and above which 50–60% of patients developed Grade 3+ toxicity. The volume of small bowel receiving at least 15 Gy ( V 15) was strongly associated with the degree of toxicity. Univariate analysis of patient and treatment-related factors revealed no other significant predictors of severe toxicity. Conclusions: A strong dose-volume relationship exists for the development of Grade 3+ acute small bowel toxicity in patients receiving concurrent 5-FU-based chemoradiotherapy for rectal carcinoma.

Preliminary report of toxicity following 3D radiation therapy for prostate cancer on 3DOG/RTOG 9406

Purpose: A prospective Phase I dose escalation study was conducted to determine the maximally-tolerated radiation dose in men treated with three-dimensional conformal radiation therapy (3D CRT) for localized prostate cancer. This is a preliminary report of toxicity encountered on the 3DOG/RTOG 9406 study. Methods and Materials: Each participating institution was required to implement data exchange with the RTOG 3D quality assurance (QA) center at Washington University in St. Louis. 3D CRT capabilities were strictly defined within the study protocol. Patients were registered according to three stratification groups: Group 1 patients had clinically organ-confined disease (T1,2) with a calculated risk of seminal vesicle invasion of < 15%. Group 2 patients had clinical T1,2 disease with risk of SV invasion ≥ 15%. Group 3 (G3) patients had clinical local extension of tumor beyond the prostate capsule (T3). All patients were treated with 3D techniques with minimum doses prescribed to the planning target volume (PTV). The PTV margins were 5–10 mm around the prostate for patients in Group 1 and 5–10 mm around the prostate and SV for Group 2. After 55.8 Gy, the PTV was reduced in Group 2 patients to 5–10 mm around the prostate only. Minimum prescription dose began at 68.4 Gy (level I) and was escalated to 73.8 Gy (level II) and subsequently to 79.2 Gy (level III). This report describes the acute and late toxicity encountered in Group 1 and 2 patients treated to the first two study dose levels. Data from RTOG 7506 and 7706 allowed calculation of the expected probability of observing a ≥ grade 3 late effect more than 120 days after the start of treatment. RTOG toxicity scores were used. Results: Between August 23, 1994 and July 2, 1997, 304 Group 1 and 2 cases were registered; 288 cases were analyzable for toxicity. Acute toxicity was low, with 53–54% of Group 1 patients having either no or grade 1 toxicity at dose levels I and II, respectively. Sixty-two percent of Group 2 patients had either none or grade 1 toxicity at either dose level. Few patients (0–3%) experienced a grade 3 acute bowel or bladder toxicity, and there were no grade 4 or 5 toxicities. Late toxicity was very low in all patient groups. The majority (81–85%) had either no or mild grade 1 late toxicity at dose level I and II, respectively. A single late grade 3 bladder toxicity in a Group 2 patient treated to dose level II was recorded. There were no grade 4 or 5 late effects in any patient. Compared to historical RTOG controls (studies 7506, 7706) at dose level I, no grade 3 or greater late effects were observed in Group 1 and Group 2 patients when 9.1 and 4.8 events were expected ( p = 0.003 and p = 0.028), respectively. At dose level II, there were no grade 3 or greater toxicities in Group 1 patients and a single grade 3 toxicity in a Group 2 patient when 12.1 and 13.0 were expected ( p = 0.0005 and p = 0.0003), respectively. Multivariate analysis demonstrated that the relative risk of developing acute bladder toxicity was 2.13 if the percentage of the bladder receiving ≥ 65 Gy was more than 30% ( p = 0.013) and 2.01 if patients received neoadjuvant hormonal therapy ( p = 0.018). The relative risk of developing late bladder complications also increased as the percentage of the bladder receiving ≥ 65 Gy increased ( p = 0.026). Unexpectedly, there was a lower risk of late bladder complications as the mean dose to the bladder and prescription dose level increased. This probably reflects improvement in conformal techniques as the study matured. There was a 2.1 relative risk of developing a late bowel complication if the total rectal volume on the planning CT scan exceeded 100 cc ( p = 0.019). Conclusion: Tolerance to high-dose 3D CRT has been better than expected in this dose escalation trial for Stage T1,2 prostate cancer compared to low-dose RTOG historical experience. With strict quality assurance standards and review, 3D CRT can be safely studied in a cooperative group setting. There appears to be a dose-volume relationship with respect to the development of both acute and late bladder toxicities. Whether improvement in efficacy can be gained with this treatment approach will await a prospective randomized trial. Meanwhile, the innovative image/clinical database resulting from this trial will serve as an important resource in the study of late effects and tumor control.

A Pilot Study of Continuous, Hyperfractionated, Accelerated Radiotherapy in Rectal Adenocarcinoma

This pilot study investigated the feasibility, toxicity and effect of continuous, hyperfractionated, accelerated radiotherapy (CHART) in 19 patients with adenocarcinoma of the rectum who were treated at Mount Vernon Hospital between April 1992 and April 1994. A total dose of 54Gy was given in 36 fractions over 12 consecutive days; three fractions of 1.5Gy were employed each day with an interfraction interval of 6 hours.Of these 19 patients, 13 had local pelvic recurrence from rectal carcinoma, four had a primary rectal carcinoma (which was unsuitable for abdominoperineal resection because of patient frailty), and two had large, fixed, unresectable tumours and were given radiotherapy preoperatively to a lower dose of 42Gy in 28 fractions over 10 days to facilitate surgery. However, none of the 19 patients subsequently underwent surgical resection.Treatment compliance with radiotherapy was 95%. Acute bowel toxicity was assessed by means of a daily bowel chart for 6 weeks and then at 8, 12 and 26 weeks after the completion of radiotherapy. Patients were subsequently scored using the World Health Organization (WHO) grading system. No toxic deaths were observed in this study. There were five grade 3 and one grade 4 toxicities (WHO scale) observed in six patients. There has been minimal acute bladder toxicity in two patients and skin reactions have been surprisingly minimal in all but three patients. Small bowel obstruction and late bowel damage, possibly attributable to radiotherapy, occurred in three patients.Complete pain relief was achieved in recurrent rectal cancer in 100% of patients, at a median of 15 days since commencing radiotherapy (range 7–63 days), and has been maintained for mean and median durations of 19 and 18 months respectively (range 1.5–45 months). Five patients have had a recurrence of pain at 3, 4, 8, 9 and 18 months respectively. All four patients with primary rectal adenocarcinoma achieved a complete response, which has been sustained for 4 months (until death), 54 and 57 months, although one patient relapsed locally at 8 months.In summary, CHART appears to be a feasible treatment for pelvic tumours with regard to toxicity. Patients with pain from a locoregional recurrence achieved rapid complete pain relief, which was sustained for many months.

Adjuvant and neoadjuvant chemoradiation therapy for primary colorectal cancer

The management of rectal cancer presents substantial challenges. Patients with T3 and/or node-positive rectal cancers are at high risk for local failure and distant metastases (DM). Adjuvant radiation has been shown to decrease local recurrence (LR) rates; however, this local therapy has not been demonstrated to improve survival when compared to surgery alone. In several prospective randomized trials adjuvant chemoradiation with 5-fluorouracil-(5-FU)-based chemotherapy improved LR rates, DM rates, and overall survival (OS). The optimal chemotherapeutic regimen has not been determined; however, studies comparing standard IV bolus 5-FU administration with continuous infusion (CI) 5-FU demonstrated that CI administration was superior. Preoperative therapy has potential advantages over adjuvant therapy such as less acute bowel toxicity and improved sphincter preservation. Preoperative chemoradiation has been shown in several studies to improve LR rates and OS when compared to surgery alone. Our current approach to patients with resectable T3 or N1 cancer in the distal two-thirds of the rectum on preoperative staging is preoperative chemoradiation with planned postoperative chemotherapy. This regimen offers the best chance for local control and disease-free survival while potentially downstaging the tumor and improving sphincter preservation.

A feasibility study of accelerated fractionation in radiotherapy of carcinoma of the urinary bladder

Purpose : To establish the shortest possible overall treatment time, with respect to acute and late toxicity, in which a radiation dose of 66 Gy in 2 Gy/fraction can be administered to the urinary bladder. Methods and Materials : In a stepwise fashion the overall treatment time of our routinely used conventional treatment schedule (66 Gy in 2 Gy/fraction in 6.5 weeks) was reduced to 5 weeks (Step 1) and then 4 weeks (Step 2). Shortening of the overall treatment time was obtained by giving two daily fractions during the last part of the treatment. The interfraction interval was a minimum of 6 h. Toxicity was scored according to a modified scheme of the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer. Fifteen patients received the 5-week schedule and 25 patients received the 4-week schedule. Results : Note that feasibility was very good for the 5-week schedule. No Grade ≥3 acute bowel or bladder toxicity was seen in these patients. Severe late complications did not occur. In the 4-week schedule, acute bladder toxicity was unaffected but acute bowel toxicity was considerably increased. Of the 25 patients, 16 suffered from Grade 3 toxicity, 3 from Grade 4, and 1 from Grade 5 toxicity. Actuarial analysis at 3 years showed a 31% incidence of Grade 4 late bladder complications. Conclusion : It is concluded that the 5-week schedule is well tolerated. In contrast, the 4-week schedule shows unacceptable acute bowel toxicity and an increased incidence of late bladder comlications ( p = 0.043).

362Prevention of acute small bowel toxicity, in pelvic radiotherapy by a specific computerized diet-therapy. Results of multicentric randomized trial

362Prevention of acute small bowel toxicity, in pelvic radiotherapy by a specific computerized diet-therapy. Results of multicentric randomized trial

Phase II Study to Evaluate the Toxicity and Efficacy of Concurrent Cisplatin and Radiation Therapy in the Treatment of Patients with Locally Advanced Squamous Cell Carcinoma of the Cervix

Sixty patients presenting with poor prognosis squamous cell cancer of the cervix have been studied in a phase II clinical trial. Patients were treated with radiotherapy and concurrent cisplatin chemotherapy every 10 days. Treatment was well tolerated with all patients completing radiotherapy as prescribed. There was one case of grade 4 acute bowel toxicity. Significant late morbidity was acceptable for this group of patients being restricted to two cases (3.3%) of grade 4 toxicity to the bowel. Pelvic control rates of 78% have been observed. There have been no pelvic recurrences after 26 months, although recurrences beyond the pelvis have occurred up to 4 years later. Actuarial 4-year survival is encouraging at 60%.