High-dose Preoperative Radiation Research Articles

Stereotactic Body radiotherapy and pedicLE screw fixatioN During one hospital visit for patients with symptomatic unstable spinal metastases: a randomized trial (BLEND RCT) using the Trials within Cohorts (TwiCs) design

BackgroundSpinal metastases can lead to unremitting pain and neurological deficits, which substantially impair daily functioning and quality of life. Patients with unstable spinal metastases receive surgical stabilization followed by palliative radiotherapy as soon as wound healing allows. The time between surgery and radiotherapy delays improvement of mobility, radiotherapy-induced pain relief, local tumor control, and restart of systemic oncological therapy. Stereotactic body radiotherapy (SBRT) enables delivery of preoperative high-dose radiotherapy while dose-sparing the surgical field, allowing stabilizing surgery within only hours. Patients may experience earlier recovery of mobility, regression of pain, and return to systemic oncological therapy. The BLEND RCT evaluates the effectiveness of SBRT followed by surgery within 24 h for the treatment of symptomatic, unstable spinal metastases.MethodsThis phase III randomized controlled trial is embedded within the PRospective Evaluation of interventional StudiEs on boNe meTastases (PRESENT) cohort. Patients with symptomatic, unstable spinal metastases requiring stabilizing surgery and radiotherapy will be randomized (1:1). The intervention group (n = 50) will be offered same-day SBRT and surgery, which they can accept or refuse. According to the Trial within Cohorts (TwiCs) design, the control group (n = 50) will not be informed and receive standard treatment (surgery followed by conventional radiotherapy after 1–2 weeks when wound healing allows). Baseline characteristics and outcome measures will be captured within PRESENT. The primary outcome is physical functioning (EORTC-QLQ-C15-PAL) 4 weeks after start of treatment. Secondary endpoints include pain response, time until return to systemic oncological therapy, quality of life, local tumor control, and adverse events up to 3 months post-treatment.DiscussionThe BLEND RCT evaluates the effect of same-day SBRT and stabilizing surgery for the treatment of symptomatic, unstable spinal metastases compared with standard of care. We expect better functional outcomes, faster pain relief, and continuation of systemic oncological therapy. The TwiCs design enables efficient recruitment within an ongoing cohort, as well as prevention of disappointment bias and drop-out as control patients will not be informed about the trial.Trial registrationClinicalTrials.gov NCT05575323. Registered on October 11, 2022.

Treatment of rectal cancer by transanal endoscopic microsurgery: experience with 425 patients.

To describe our experience in treating rectal cancer by transanal endoscopic microsurgery (TEM), report morbidity and mortality and oncological outcome. A total of 425 patients with rectal cancer (120 T1, 185 T2, 120 T3 lesions) were staged by digital rectal examination, rectoscopy, transanal endosonography, magnetic resonance imaging and/or computed tomography. Patients with T1-N0 lesions and favourable histological features underwent TEM immediately. Patients with preoperative stage T2-T3-N0 underwent preoperative high-dose radiotherapy; from 1997 those aged less than 70 years and in good general health also underwent preoperative chemotherapy. Patients with T2-T3-N0 lesions were restaged 30 d after radiotherapy and were then operated on 40-50 d after neoadjuvant therapy. The instrumentation designed by Buess was used for all procedures. There were neither perioperative mortality nor intraoperative complications. Conversion to other surgical procedures was never required. Major complications (urethral lesions, perianal or retroperitoneal phlegmon and rectovaginal fistula) occurred in six (1.4%) patients and minor complications (partial suture line dehiscence, stool incontinence and rectal haemorrhage) in 42 (9.9%). Postoperative pain was minimal. Definitive histological examination of the 425 malignant lesions showed 80 (18.8%) pT0, 153 (36%) pT1, 151 (35.5%) pT2, and 41 (9.6%) pT3 lesions. Eighteen (4.2%) patients (ten pT2 and eight pT3) had a local recurrence and 16 (3.8%) had distant metastasis. Cancer-specific survival rates at the end of follow-up were 100% for pT1 patients (253 mo), 93% for pT2 patients (255 mo) and 89% for pT3 patients (239 mo). TEM is a safe and effective procedure to treat rectal cancer in selected patients without evidence of nodal involvement. T2-T3 lesions require preoperative neoadjuvant therapy.

Reduction in Wound Complications With Low- Versus High-Dose Preoperative Radiation Therapy for Sacro-Coccygeal Chordomas

Reduction in Wound Complications With Low- Versus High-Dose Preoperative Radiation Therapy for Sacro-Coccygeal Chordomas

High-dose radiotherapy (60 Gy) with oral UFT/folinic acid and escalating doses of oxaliplatin in patients with non-resectable locally advanced rectal cancer (LARC): A phase I trial

Background. Consensus is that patients with locally advanced rectal cancer (LARC) should receive long-term chemoradiotherapy (CRT) before surgery. With the intent to offer the patients intensified concomitant chemotherapy (CT) to improve outcome and to assess tolerability and toxicity of oxaliplatin (Ox) a phase I trial of high dose pelvic radiotherapy (RT), fixed dose of oral UFT/l-leucovorin and increasing doses of weekly Ox were performed. Methods. Pelvic RT with 48.6 Gy/27 fractions was given to the primary tumour and the regional lymph nodes and a concurrent boost of 5.4 Gy/27 fractions with a final boost of 6 Gy/3 fractions was given to the gross tumour volume (GTV) (60 Gy/30 fractions). Concurrent with RT patients received a daily dose of UFT 300 mg/m2 plus fixed dose l-leucovorin 22.5 mg 5/7 days and increasing weekly doses of Ox with 10 mg/m2/week from a start dose of 30 mg/m2/week to a maximum of 60 mg/m2/week. In addition, before and after CRT the patients received one course of TEGAFOX (UFT 300 mg/m2 with l/leucovorin 22.5 mg Days 1–14 and Ox 130 mg/m2 given on Day 1). Surgery was planned at least six weeks after the completion of the CRT. Results. From May 2005 to March 2009, 18 patients with LARC (16 primary, two recurrent) were included in this phase I trial. Toxicity was low with only 5–17% grade 3–4 toxicity. Fifteen patients (83%) were operated (14 R0 resection and 1 R1 resection) after completion of CRT. Five (33%) patients had a pathological complete response (ypCR). When ypCR was combined with yp few residual cells, the rate was 60%. Thirteen patients are still alive December 2011. Conclusion. Preoperative high-dose RT and concomitant UFT with increasing doses of Ox up to 60 mg/m2/week was feasible with low toxicity, high ypCR rates and promising OS in patients with non-resectable LARC.

Combination Short-Course Preoperative Irradiation, Surgical Resection, and Reduced-Field High-Dose Postoperative Irradiation in the Treatment of Tumors Involving the Bone

To assess the feasibility and outcomes of combination short-course preoperative radiation, resection, and reduced-field (tumor bed without operative field coverage) high-dose postoperative radiation for patients with solid tumors mainly involving the spine and pelvis. Between 1982 and 2006, a total of 48 patients were treated using this treatment strategy for solid tumors involving bone. Radiation treatments used both photons and protons. Of those treated, 52% had chordoma, 31% had chondrosarcoma, 8% had osteosarcoma, and 4% had Ewing's sarcoma, with 71% involving the pelvis/sacrum and 21% elsewhere in the spine. Median preoperative dose was 20 Gy, with a median of 50.4 Gy postoperatively. With 31.8-month median follow-up, the 5-year overall survival (OS) rate is 65%; 5-year disease-free survival (DFS) rate, 53.8%; and 5-year local control (LC) rate, 72%. There were no significant differences in OS, DFS, and LC according to histologic characteristics. Between primary and recurrent disease, there was no significant difference in OS rates (74.4% vs. 51.4%, respectively; p = 0.128), in contrast to DFS (71.5% vs. 18.3%; p = 0.0014) and LC rates (88.9% vs. 30.9%; p = 0.0011) favoring primary disease. After resection, 10 patients experienced delayed wound healing that did not significantly impact on OS, DFS, or LC. This approach is promising for patients with bone sarcomas in which resection will likely yield close/positive margins. It appears to inhibit tumor seeding with an acceptable rate of wound-healing complications. Dose escalation is accomplished without high-dose preoperative radiation (likely associated with higher rates of acute wound healing delays) or large-field postoperative radiation only (likely associated with late normal tissue toxicity). The LC and DFS rates are substantially better for patients with primary than recurrent sarcomas.

Pre-operative chemoradiotherapy with UFT and Leucovorin in patients with advanced rectal cancer: A phase II study

Purpose The aim this study was to determine the pathologic complete response (pCR) rate defined as tumor regression grade 1 (TRG1) and toxicity profile of the combination of high-dose pre-operative radiotherapy and simultaneous UFT/leucovorin (LV) in patients with locally advanced rectal cancer. Materials/methods Eligibility included biopsy proven rectal adenocarcinoma; T3–T4 N0–N2; performance status <2 (ECOG) and adequate blood, hepatic and renal function. Treatment consisted of radiotherapy 54 Gy at 1.8 Gy/day and UFT 300 mg/m 2/day and LV 60 mg/day, given simultaneously daily for 6 weeks. Surgery was performed within 4–6 weeks period after chemoradiotherapy. Patients who did not achieve TGR1 were to receive 4 cycles of adjuvant UFT/LV on days 1–28, every 5 weeks. Results Sixty-eight patients were included. All but one received full dose of radiation and 62 had the total planned pre-operative UFT/LV dose. Grade 3 toxicities were diarrhea 7% and proctitis 3%. Complete resection was achieved in 62 patients (91%). Tumor regression grade 1 (TRG1) was seen in 11 patients (16%). Forty-eight patients received adjuvant UFT/LV. Grade 3 toxicity during adjuvant UFT/LV included diarrhea 12%, asthenia 4%, neutropenia 2%, and hand–foot syndrome 2%. The 3-year disease-free survival was 71%. Conclusions Simultaneous high-dose pre-operative localized radiation therapy concurrent with UFT/LV is feasible and has a low toxicity profile. This schedule is highly effective and merits further investigation.

Transanal endoscopic microsurgery for the treatment of selected patients with distal rectal cancer: 15 years experience

Local therapy for early rectal cancer is a valid alternative to the classical radical operation, which has a higher morbidity and mortality rate. The use of high-dose preoperative radiation appears to enhance the options for sphincter-saving surgery even for T2-T3 rectal cancer patients with effective local control. The authors report their experience with transanal endoscopic microsurgery (TEM) used to manage selected cases of distal rectal cancer without evidence of nodal or distant metastasis (N0-M0). The study enrolled 196 patients with rectal cancer (51 T1, 84 T2, and 61 T3). All the patients staged preoperatively as T2 and T3 underwent preoperative high-dose radiotherapy, and since 1997, patients younger than 70 years in good general condition also have undergone preoperative chemotherapy. Minor complications were observed in 17 patients (8.6%) and major complications in only 3 patients (1.5%). The definitive histology was 33 pT0 (17%), 73 pT1 (37%), 66 pT2 (34%), and 24 pT3 (12%). Eight patients (5 pT2 and 3 pT3) experienced local recurrence (4.1%). The rectal cancer-specific survival rate at the end of the follow-up period was 100% for pT1, 90% for pT2, and 77% for pT3 patients. Patients with T1 cancer and favorable histologic features may undergo local excision alone, whereas those with T2 and T3 rectal cancer require preoperative radiochemotherapy. The results in the authors' experience after TEM appear not to be substantially different in terms of local recurrence and survival rate from those described for conventional surgery.

The risk factors and treatment of bronchopleural fistula after pneumonectomy

To analyze the risk factors which influencing the development of bronchopleural fistula (BPF) in pulmonary resections for lung cancer. To clarify the preventive techniques and treatment strategies of BPF. Review the clinical data of 32 patients of postpneumonectomy BPF from 965 patients accepted pneumonectomy for lung cancer from May 1987 to May 2007. Univariate and multivariate analyses were performed by the logistic regression procedure to identify the significant risk factors for BPF in 965 pulmonary resections for lung cancer. The prevalence of BPF was 3.3% (32/965). BPF occurred in the right main bronchial stump in 28 patients, left main bronchial stump in 4 patients. The significant risk factors for BPF formation were right pneumonectomy, preoperative irradiation, prolonged mechanical ventilation, bronchial stump more than 2 cm and hypoalbuminemia. Multivariate analysis identified right pneumonectomy, preoperative radiotherapy and hypoalbuminemia as the risk factors of BPF. Successful closure of BPF was achieved in 13 patients (40.6%). The fistula was successfully closed in 5 of 6 patients who had received biologic glues applied bronchoscopically with a fistula less than 3 mm. Pedicled omentum was successfully used for the treatment in 5 of 6 patients with a fistula more than 3 mm. Right pneumonectomy, high-dose preoperative radiation therapy and hypoalbuminemia are risk factors for postpneumonectomy BPF. Biologic glues can be applied bronchoscopically to achieve endobronchial closure of the fistula less than 3 mm. Omentoplasty is useful for the fistula more than 3 mm.

Long-term results of a phase II trial of high-dose radiotherapy (60 Gy) and UFT/l-leucovorin in patients with non-resectable locally advanced rectal cancer (LARC)

Background. Preoperative radiochemotherapy is a cornerstone in patients with non- resectable locally advanced rectal cancer (LARC). To improve outcome (number of R0 resections and survival) high-dose radiotherapy (RT) was combined with oral UFT/l-leucovorin to allow tumour regression before radical intended surgery. Methods. Pelvic RT was delivered with megavoltage photons using a 5 field technique. RT was CT-based, given 5 days a week through one posterior field and two lateral fields (48.6 Gy/27 fractions) to encompass the primary tumour and the regional lymph nodes. In addition, the tumour bed received a concurrent boost (5.4 Gy/27 fractions) and a final boost (6 Gy/3 fractions); thus GTV received 60 Gy/30 fractions. Concurrent with RT patients received a daily dose of oral UFT 300 mg/m2 plus l-leucovorin 22.5 mg 5/7days (divided in three doses). Results. From September 2000 to November 2004, 52 patients (median age 60 years (32–83); median PS 0 (0–2)) with LARC (36 primary, 16 recurrent) were included in this phase II study. All but three patients received the planned 60 Gy, median duration of RT was 42 days (25–49). Toxicity was very modest; only four patients had a dose reduction of UFT. No hematological toxicity of clinical significance was seen. Non-hematological toxicity grade 1 (GI-toxicity, fatigue and/or dysuria) was frequently observed but only four patients experienced grade 3 toxicity (diarrhoea and/or nausea/vomiting). Forty patients (77%) were operated (30 R0, 5 R1, 5 R2) median 55 days (27–112) after completion of RT. Seven (13%) patients had a pathological complete response (pCR). Thirty-one patients (60%) died after median 25.4 months (1.6–45.2 months). Twenty-one patients (40%) are still alive June 2007. Conclusions. Preoperative high-dose RT and concomitant UFT produces major regression in most patients with non-resectable LARC and thus a good chance of cure.

Postoperative mortality in rectal cancer treated with or without preoperative radiotherapy: causes and risk factors.

Adjuvant preoperative radiotherapy in patients with rectal cancer improves local control and possibly overall survival. However, an increased postoperative mortality rate after radiotherapy has been observed in some trials. This study was based on 1399 patients in two randomized trials of radiotherapy. It reviewed the causes of death after operation and attempted to identify risk factors for postoperative mortality in patients with rectal cancer treated with or without high-dose (5 x 5 Gy) preoperative radiotherapy. The majority of deaths were from cardiovascular disease or infection. The risk of postoperative mortality was significantly increased in patients irradiated with a two-portal technique to a relatively large volume compared with those not given radiotherapy, but not in those irradiated with a four-portal technique to a limited volume. Age, sex, tumour stage and coexistent cardiovascular disease were independent risk factors for postoperative mortality. The risk of postoperative death in patients with rectal cancer is related to the preoperative radiotherapy technique.

Conservative treatment for low rectal carcinoma by local excision with or without radiotherapy.

Thirty-seven patients with low rectal carcinoma were treated by transanal resection between January 1979 and December 1988. Adjuvant radiotherapy was used in eight patients before operation, in 13 after operation and six patients had both preoperative and postoperative radiotherapy. The selection criteria for transanal resection were low, superficial tumours treated conservatively with curative intent (group 1, 18 patients) or patients medically unfit for (12) or refusing (seven) abdominoperineal resection (APR) (group 2, 19 patients). In group 1, the local recurrence rate was 11 per cent with an overall 5-year survival rate of 100 per cent. In group 2, the local recurrence rate was 53 per cent with an overall 5-year survival rate of 35 per cent. There was no postoperative mortality and minimal morbidity. Salvage of local failure was by APR in six patients. The survival rate after local recurrence was 70 per cent at 1 year and 30 per cent at 5 years. Transanal resection can be proposed as a curative procedure for selected low, small, minimally infiltrating and well differentiated adenocarcinomas. Local control might be improved by postoperative radiotherapy for Astler-Coller stage B1 tumours or those above 3 cm in diameter. Further trials should examine the results of high-dose (60 Gy) preoperative radiotherapy so that transanal resection might be employed for favourable post-irradiation stage (0 or A) lesions. This new strategy will benefit from a better evaluation of tumour response after primary radiotherapy and an improved assessment of histological excision margins.

Long-term results in patients with T2–3 N0 distal rectal cancer undergoing radiotherapy before transanal endoscopic microsurgery

Local excision after radiotherapy for node-negative low rectal cancer may be an alternative to radical excision. This study evaluated the results of local excision in patients with small (less than 3 cm in diameter) T2 and T3 distal rectal tumours following neoadjuvant therapy. One hundred patients with rectal cancer (54 uT2 and 46 uT3 uN0 tumours) were enrolled. All patients underwent preoperative radiotherapy followed by local excision by means of transanal endoscopic microsurgery. Definitive histological examination revealed nine pT1, 54 pT2 and 19 pT3 tumours. A complete response (R0) or microscopic residual tumour (R1mic) was found in three and 15 patients respectively. Minor complications occurred in 11 patients and major complications in two. At a median follow-up of 55 (range 7-120) months, the local failure rate was 5 per cent and metastatic disease was found in two patients. The cancer-specific survival rate at 90 months' follow-up was 89 per cent, and the overall survival rate 72 per cent. Salvage abdominoperineal resection was performed in three patients, two of whom were disease free at 15 and 19 months. Treatment of small uT2 and uT3 uN0 rectal cancers with preoperative high-dose radiotherapy followed by transanal endoscopic microsurgery is an acceptable alternative to conventional radical resection.

Short-term preoperative radiotherapy is a safe approach for treatment of locally advanced rectal cancer

The Swedish Rectal Cancer Trial (SRCT) demonstrated that a short term regimen of high-dose preoperative radiotherapy (5x5 Gy) not only reduces the risk of local recurrence but also improves overall survival rate. An increase in postoperative mortality and morbidity has also been observed, however. We therefore evaluated early postoperative complications in patients treated with neoadjuvant radiotherapy for locally advanced rectal adenocarcinoma. Between 2000 and 2004, 85 patients with locally advanced rectal tumors were treated in our institution. Preoperative staging was based on CT scan and, in several cases, on endorectal ultrasonography. They were 55 men and 30 women, with a median age of 68 years. They were retrospectively divided into two groups: Group A, which included 40 patients undergoing preoperative radiotherapy (25 Gy in five fractions) followed by surgery within 1 week, and Group B, which included 45 patients with rectal cancer receiving surgery immediately after diagnosis. Both groups were homogeneous regarding age, gender and preoperative stage of the disease. The two groups were compared for both technical difficulties during operation and rate of postoperative complications. No postoperative deaths were recorded in either group. Low anterior resection with total mesorectal excision was performed in all group A patients, whereas eight patients in group B underwent abdominoperineal resection (P<0.05). Diverting stoma was performed in seven patients of group A and it was closed 3-6 months later on every occasion. Postoperative morbidity was not statistically significant between the two groups (40 vs 39%). The rate of postoperative hemorrhage, pelvic or abdominal wound infection, acute urinary infection, and delayed ileus was similar. The percentage of major anastomotic leak was also equivalent (5 vs 6.6%). Short-term preoperative radiotherapy does not increase the rate of postoperative complications and is a safe therapeutic adjunct for the treatment of locally advanced rectal cancer.

Primary rectus abdominis myocutaneous flap for repair of perineal and vaginal defects after extended abdominoperineal resection

Significant morbidity can result from perineal wounds, particularly after radiotherapy and extensive resection for cancer. Myocutaneous flaps have been used to improve healing. The purpose of this study was to evaluate the morbidity and results of primary rectus abdominis myocutaneous flap reconstruction of the vagina and perineum after extended abdominoperineal resection. Thirty-one consecutive patients undergoing one-stage rectus abdominis myocutaneous flap reconstruction of extensive perineal wounds were studied prospectively. Twenty-six patients had surgery for recurrent or persistent epidermoid anal cancer or low rectal cancer, and 21 had high-dose preoperative radiotherapy. Three weeks after the operation, complete healing of the perineal wound was seen in 27 of the 31 patients. There were nine flap-related complications including three patients with partial flap necrosis, two with vaginal stenosis, one with vaginal scarring, one with small flap disunion and two with weakness of the anterior abdominal wall. There were no unhealed wounds at the completion of follow-up (median 9 months). The transpelvic rectus abdominis myocutaneous flap for the reconstruction of large perineal and vaginal wounds achieves wound healing with only moderate morbidity in the majority of patients after extensive abdominoperineal resection with or without radiotherapy.

Localized radiation therapy and simultaneous chemotherapy with uft and low-dose leucovorin as neoadjuvant treatment in-patients with T3-T4 rectal cancer. a phase II study

The aim of the study was to determine pathologic complete response rate and toxicity profile of the combination of high-dose preoperative localized radiation therapy and chemotherapy with UFT and leucovorin given simultaneously in patients with T3-T4 rectal cancer. This combination has been demonstrated feasible in a previous phase I study (Hoff, et al, JCO 18: 3529–3534, 2000). Secondary objectives were to assess resectability and sphincter preservation rates. Eligibility included biopsy proven of rectal adenocarcinoma, T3-T4,N0-2,M0 lesions, performance status <2 (ECOG) and adequate liver, renal, hematological and cardiac functions. Staging work-up included colonoscopy or barium enema, chest X-ray, abdominopelvic CT and transrectal ultrasonography. Treatment consisted of radiation therapy at two dose levels: a)PTV1: GTV + 3–5 cm margin, TD 45 Gy at 1.8 Gy/d b)PTV2: GTV + 1–2 cm margin, TD 55 Gy at 2 Gy/d and simultaneously UFT 300 mg/m2/d and leucovorin 60 mg/d, daily during 6 weeks given orally. Surgical resection was performed within 4–6 weeks after treatment. Between January 2001 and November 2003, 40 patients were included into this study. Patients characteristics: age 35–79 (median 64.5); male/female 29/11; T3N0:23, T3N1:15, and T4N1:2. Thirty-seven patients received full dose of radiation (93%) and in one patient UFT was reduced to 150 mg/m2/d. Mean treatment time was 52 days (range 37–62). Overall, 7 patients (17.5%) had grade 3 acute toxicity being mucositis in 4 patients (10%) and anusitis in 3 (7.5%). There was no grade 4 toxicity. Only one patient developed grade 2 neutropenia. Mean time between radiochemotherapy and surgery was 37 days (range 31–55). At the time of analysis, 3 patients are in surgery and therefore are not evaluable for response. Of the 37 remaining patients, 8 achieved pathologic complete response (21,6%) and 20 downstaged (54%). There was microscopical residual tumor in 8 patients. Radical surgery with free margins could be performed in all 37 patients, being sphincter-saving procedures in 3 of the 9 patients with tumor <5 cm from anal verge. Simultaneous high-dose preoperative localized radiation therapy and UFT and leucovorin is feasible with a low toxicity profile. This schedule is highly effective and merits further investigation

Localized radiation therapy and simultaneous chemotherapy with uft and low-dose leucovorin as neoadjuvant treatment in-patients with T3-T4 rectal cancer. a phase II study

The aim of the study was to determine pathologic complete response rate and toxicity profile of the combination of high-dose preoperative localized radiation therapy and chemotherapy with UFT and leucovorin given simultaneously in patients with T3-T4 rectal cancer. This combination has been demonstrated feasible in a previous phase I study (Hoff, et al, JCO 18: 3529–3534, 2000). Secondary objectives were to assess resectability and sphincter preservation rates.

The adequacy of distal surgical margin following high dose preoperative radiation and sphincter preservation surgery for rectal cancer

Purpose/Objective: Preoperative radiation is being utilized extensively in the treatment of rectal cancer. However, the adequacy of distal surgical margin following High Dose preoperative radiation and sphincter preservation surgery for rectal cancer remains to be established. This study was undertaken to examine the impact of the length of distal surgical margins on local recurrence following sphincter preservation surgery for rectal cancer.

Improved sphincter preservation of low rectal cancer with high dose preoperative radiotherapy: the lyon R96-02 randomized trial

Purpose The potential advantage of high-dose preoperative radiotherapy to increase tumor response and improve the chance of sphincter preservation for low rectal cancer remains controversial. The aim of this trial was to evaluate the role of escalating the dose of preoperative radiation to increase sphincter-saving procedures. Patients and Methods Patients with rectal carcinoma located in the lower rectum, staged T2 or T3, Nx, or MO with endorectal sonography, and not involving more than two-thirds circumference, were randomly assigned to one of two groups: preoperative external-beam radiotherapy (EBRT; 39 Gy in 13 fractions over 17 days) versus the same EBRT with boost (85 Gy in three fractions) using endocavitary contact x-ray. Results Between 1996 and 2001, 88 patients were enrolled onto the study. A significant improvement was seen in favor of the contact x-ray boost for complete clinical response (24% v 2%) and for a complete or near-complete sterilization of the operative specimen (57% v 34%). A significant increase in sphincter preservation was observed in the boost group (76% v 44%; P = .004). At a median follow-up of 35 months, there was no difference in morbidity, local relapse, and 2-year overall survival. Conclusion A dose escalation with endocavitary irradiation provides increased tumor response and sphincter preservation with no detrimental effect on treatment toxicity and early clinical outcome.

Long-term results of patients with pT2 rectal cancer treated with radiotherapy and transanal endoscopic microsurgical excision.

Anterior resection and abdomino-perineal resection are the surgical techniques used most frequently in the treatment of rectal cancer. Local recurrence rates of 10% to 14% are described after these conventional procedures. Preoperative neoadjuvant radiotherapy reduces local failure. Because local excision techniques can be applied to treat early rectal cancer in selected patients, we evaluated the results of preoperative high-dose radiotherapy and transanal endoscopic microsurgical excision (TEM) in patients with T2 rectal cancer. All patients underwent preoperative irradiation with 5,040 cGy, divided over 5 weeks. Forty days after completion of radiotherapy, the patients underwent complete full-thickness local excision of the rectal lesion including adjacent perirectal fat by TEM. The patients were followed for up to 8 years. Thirty-five patients, with pT2 rectal cancer as determined by pathological examination of the surgical specimen were enrolled in the present study. The tumors were responsive to preoperative radiotherapy in 82.8% of cases. No intraoperative complications and no conversion to open surgery were observed. No major complications and no mortality occurred during the 60-day postoperative period. Minor postoperative complications were observed in 5 patients (14.3%). The median follow-up of the patients was 38 months (range 24 to 96 months). One local recurrence (2.85%) was noted. The probability of surviving at 96 months after completion of treatment was 83%. Local excision by TEM combined with preoperative high-dose radiotherapy can achieve results similar to those observed after conventional surgery in patients with pT2 rectal cancer.

Effect of preoperative radiotherapy on matrilysin gene expression in rectal cancer

Matrilysin, a member of matrix metalloproteinase family, is believed to play a significant role in the growth and proliferation of colon cancer cells. Overexpression of the matrilysin gene has been shown to correlate with Dukes' stage and increased metastatic potential in colorectal cancer. The aim of this study was to evaluate the effect of preoperative high-dose radiotherapy (25 Gy in five fractions over 5 days) on matrilysin (MMP-7) gene expression, in patients with resectable rectal cancer, by a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Biopsy samples of tumour (n=30) and distant normal mucosa (n=12) from 15 patients were obtained pre- and post-radiotherapy. Messenger (m)RNA was extracted from all of the tissue samples and reverse transcribed to double-stranded cDNA. Quantitative RT-PCR was performed to study the effect of preoperative radiotherapy on matrilysin gene expression in both the tumour and normal mucosal specimens. Matrilysin mRNA values were expressed relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for each sample. In 14 out of 15 cases, matrilysin mRNA was detected in the cancerous tissue. Although all six normal mucosal specimens expressed matrilysin mRNA, the levels were approximately 10-fold lower compared with those seen in the paired tumour samples. Preoperative radiotherapy led to a significant 6- to 7-fold increase (P=0.001) in the expression of matrilysin mRNA in rectal cancer tissue. In contrast, there was no significant change in the matrilysin mRNA expression of normal mucosal specimens post-radiotherapy. Preoperative high-dose radiotherapy upregulates matrilysin gene expression in rectal cancer. Matrilysin inhibition may be a useful preventive or therapeutic adjunct to radiotherapy in rectal cancer.