High-dose-rate brachytherapy without external beam irradiation for locally advanced prostate cancer.

BACKGROUND AND PURPOSE: High-dose-rate brachytherapy (HDR-BT) had been used only in combination with external beam irradiation (EBI) until our previously reported first trial of HDR-BT alone without EBI. The purpose of the current report is to evaluate the feasibility, toxicity and efficacy of this regimen, with more patient accrual and longer follow-up. MATERIAL AND METHODS: From 1995 through 2004, 111 patients with localized prostate cancer were treated with HDR-BT without EBI. Fifteen patients were considered as low-risk, 28 as intermediate-risk, and 68 as high-risk. The prescribed dose was 48 Gy/8 fractions/5 days or 54 Gy/9 fractions/5 days. Median follow-up time was 27 months (range 5-119). RESULTS: All the patients completed the treatment regimen. The 3- and 5-year PSA failure-free rates were 83% and 70%, and the local control rates 100% and 97%. The maximum toxicities observed were Grade 3 by CTCAE v3.0 (6 acute, 1 chronic). CONCLUSIONS: HDR-BT without EBI was feasible and its toxicity acceptable. Short-term tumor control was promising, even for locally advanced cases. More patient accrual and longer follow-up are needed to confirm the efficacy of this novel approach.     

External beam versus intraoperative and external beam irradiation for locally advanced pancreatic cancer

One hundred fifty-nine patients with unresectable but localized pancreatic cancer, as defined at exploratory laparotomy, were treated at the Mayo Clinic between February 1974 to April 1985. Postoperative therapy consisted of 4000 to 6000 cGy external beam irradiation (XRT) alone in 122 patients or 4500 to 5500 cGy XRT in combination with an intraoperative electron boost in 37. In addition, 132 (both groups) received 5-fluorouracil (5-FU) chemotherapy. Local control (LC) at 1 year was 82% with XRT + intraoperative radiation therapy (IORT) versus 48% with XRT and 66% versus 20% at 2 years respectively (P less than 0.0005). Due to the high incidence of hematogenous and/or peritoneal spread in both groups (abdominal failure in 54 and 56% of patients at risk), the decreased frequency of local progression did not translate into an improved survival. Neither median nor long-term survival of the two treatment groups (XRT versus XRT + IORT) was statistically different (median 12.6 months versus 13.4 months, P = 0.25). With tumor arising in the head of the pancreas, survival at 2 years was 18% as opposed to 0% for other locations (P less than 0.01). On the basis of a Cox multivariate analysis, no other treatment or prognostic factor significantly altered survival. Until the problem with systemic failure (usually abdominal) can be resolved, the median and long-term survival of patients with pancreatic carcinoma is likely to remain unchanged. Since IORT appears to improve local control, we will continue to utilize IORT in phase 1, 2 studies which also attempt to decrease the incidence of abdominal failures. Even with IORT + XRT combinations, the incidence of local progression is excessive and radiation dose modifiers need to be evaluated.     

Phase II study of a four-week hypofractionated external beam radiotherapy regimen for prostate cancer: report on acute toxicity.

PURPOSE: To evaluate the early side effects of a short course hypofractionated radiotherapy regimen in prostate cancer. MATERIALS AND METHODS: Three institutions (IRE, AZ VUB, GUH) included 36 patients with T1-T3N0M0 prostate cancer in a phase II study. Patients were treated with 56 Gy in 16 fractions over 4 weeks. Early side effects were scored using the RTOG/EORTC criteria and the international prostate symptom index (IPSI) weekly during treatment and 1 and 2 months afterwards. The results were compared with two control groups of patients previously treated with conventional fractionation at AZ VUB (238 patients) and GUH (114 patients). RESULTS: None of the patients experienced grade 3-4 toxicity. Grade 1-2 Gastro-intestinal (GI), grade 2 GI, grade 1-2 Genito-urinary (GU) and grade 2 GU toxicity occurred in 75%, 36%, 75% and 44% for the hypofractionation schedule. The corresponding figures were 25-44%, 6-29%, 47-53% and 16-44% for the control groups (p<0.01 for grade 1-2 GI and GU toxicity). Two months after treatment all GU and the majority of GI symptoms had resolved. The IPSI increased from (average +/-1 SD) 5.6+/-4 pre-treatment to 10.0+/-6 during week 2-4 and had normalized (5.2+/-4) two months after treatment. CONCLUSIONS: Though no grade 3-4 side effects were observed, the investigated schedule results in a marked increase of grade 1-2 early side effects as compared to a conventional regimen. Side effects resolved within two months post-treatment.     

Intraoperative and external beam irradiation +/- 5-FU for locally advanced pancreatic cancer

Because of the poor local control rates obtained with external beam irradiation +/- chemotherapy for locally advanced pancreatic cancer, our institution has used intraoperative radiation therapy (IORT) with electrons to deliver a single "boost" dose of radiation in 52 patients with biopsy-proven adenocarcinoma (primary, unresectable-49; primary, residual-2; and recurrent, unresectable-1). Patients received 4500-5000 rad of fractionated external beam irradiation and an IORT dose of 1750 rad (2 patients) or 2000 rad (50 patients). Acute and chronic tolerance have been acceptable. Documented local progression within either the external beam or IORT fields has been infrequent (3 of 42 evaluable patients or 7%), but there has been little, if any, change in median or long-term survival from that seen in external beam series. This is probably because of a high incidence of liver and peritoneal metastases with pancreatic cancer. A phase II pilot trial, which combines upper or total abdominal irradiation and infusion 5-FU with tumor nodal irradiation plus IORT, is in progress in our institution to evaluate tolerance and the relative incidence of abdominal failures.     

Combination chemotherapy for locally advanced pancreatic cancer: equivalence to external beam irradiation and implication for future management

Chemotherapy with 5-fluorouracil, doxorubicin, and mitomycin-C was administered to 17 patients with locally advanced pancreatic cancer. The median survival for these patients was 8 months. With a multiaxial retrospective analysis, the overall survival of this study group appears to be least equivalent to that reported with 6,000 photon rad alone or of neutrons, and compares favorably to that achieved with combined 6,000 photo rad plus 5-fluorouracil. Of 15 relapses, only 4 had presented with evidence of disseminated disease. Based upon this analysis we recommend additional studies of combination chemotherapy with radiation therapy in future prospective randomized trials.     

Efficacy of irradiation and external hyperthermia in locally advanced, hormone-refractory or radiation recurrent prostate cancer: a preliminary report

PURPOSE: To present a preliminary report on the feasibility, efficacy, and toxicity of irradiation (RT) and hyperthermia (HT) in patients with locally advanced, hormone-refractory prostate cancer (LAHRPC) who may or may not have received prior RT. METHODS AND MATERIALS: Between 1997 and 2002, 13 consecutive patients with LAHRPC or RT-recurrent prostate cancer were treated with RT and HT on a Phase I-II protocol. Eight patients had RT-recurrent LAHRPC (Group A) and 5 had LAHRPC without prior RT (Group B). All patients had large and clinically symptomatic tumors. The median RT dose was 39.6 Gy and 66.6 Gy in Groups A and B, respectively. External deep HT was delivered using a BSD-2000 Sigma-60 applicator. The median number of HT treatments was 8 in group A and 10 in group B. RESULTS: The median follow-up was 14 and 13 months for Groups A and B, respectively. All patients achieved a complete or partial response (CR/PR) and complete palliation of symptoms. Eleven patients had follow-up CT scans that demonstrated a CR in six and a PR in five. Two patients, who died of metastasis, did not have CT scans and had a PR on digital rectal examination. Two patients demonstrated a biochemical CR. The median duration of the CR/PR among Group A patients was 12 months after therapy. Three patients in Group A developed tumor recurrence at 9, 17, and 27 months after repeat RT to doses of 39.6, 36, and 50 Gy, respectively. At last follow-up, no Group B patient developed local recurrence. Grade 1-2 rectal bleeding was noted in 3 patients. RT and HT were generally well tolerated by all patients who had not previously undergone RT. Of the 8 patients who had, 6 (75%) tolerated retreatment well with minimal or no complications. Two patients in the repeat RT group had severe complications. One patient with lymphoma and factor XI deficiency developed Grade 4 hemorrhagic cystitis. Another previously irradiated patient developed a rectovesical fistula 4 months after retreatment, after disappearance of a large, invasive, and necrotic tumor. CONCLUSION: This preliminary report demonstrates the feasibility and efficacy of RT and HT in patients with LAHRPC, who may or may not have received prior RT. Presently, such patients who have undergone previous RT have no effective treatment options. RT and HT were generally well tolerated by patients who were not previously undergone RT. Of those who had been, most (6 of 8) tolerated retreatment well with minimal or no complications. The high-risk factors for treatment- and tumor regression-related side effects include the presence of large necrotic tumors, previous RT with a large dose/fraction, and the presence of bleeding disorders. Despite the size of these large tumors, RT and HT resulted in significant tumor shrinkage, rapid serum prostate-specific antigen decline, durable treatment responses, and durable palliation of symptoms. Additional clinical studies are warranted.     

Intensity Modulated Radiotherapy (IMRT) in locally advanced thyroid cancer: acute toxicity results of a phase I study.

BACKGROUND AND PURPOSE: This phase 1 study was designed to determine the toxicity of accelerated fractionation IMRT in locally advanced thyroid cancer. METHODS: Patients with high risk locally advanced thyroid cancer who required post-operative EBRT were recruited. A single-phase inverse-planned-simultaneous-boost was delivered by IMRT: 58.8 Gy/28F (daily) to the primary tumour and involved nodes and 50 Gy/28F to the elective nodes. Acute (NCICTCv.2.0) and late toxicity (RTOG and modified LENTSOM) was collected. RESULTS: Thirteen patients were treated (7 medullary thyroid, 2 Hurthle cell and 4 well differentiated thyroid cancer). G3 and G2 radiation dermatitis rates were 38.5% and 31%; G3 and G2 mucositis rates 8% and 53% and G3 and G2 pain 23% and 54%. Thirty-one percentage required enteral feeding. G3 and G2 xerostomia rates were 0% and 31%. Recovery was seen, with 62% patients having dysphagia G< or =1 2 months after IMRT. Thirty percent of patients developed L'Hermitte's syndrome. No grade 4 toxicity was observed. No dose limiting toxicity was found. CONCLUSIONS: Accelerated fractionation IMRT in this group of patients is feasible and safe. The acute toxicity appeared acceptable and early indicators of late toxicity moderate and similar to what would be expected with conventional RT. Longer follow up is required to quantify late side effects.     

Chemoradiotherapy as preoperative treatment in locally advanced unresectable pancreatic cancer patients: results of a feasibility study.

PURPOSE: The combination of radiotherapy and fluorouracil (5-FU) in patients with locally unresectable pancreatic carcinoma has led to a significant increase in survival in comparison with radiotherapy alone. Doxifluridine (5-DFUR) is an orally active fluoropyrimidine, and its cytotoxic metabolite (5-FU) may concentrate in areas of high tumor vascularization. This trial was carried out with the aims of improving locoregional control and making lesions resectable in patients with unresectable pancreatic cancer. METHODS: 5-DFUR was given at a dose of 500 mg/m2 b.i.d. by way of mouth for 4 days every other week for a total of four courses, with leucovorin 25 mg b.i.d. orally being given 2 hours before each 5-DFUR administration. External beam RT was administered at a dose of 1000 cGy per week for 3 weeks, followed by a 2-week break and then by 1000 cGy per week for a further 2 weeks (a total dose of 5000 cGy). The patients were restaged 4 weeks after the end of treatment and explored for resection in cases of partial response (PR). RESULTS: A total of 32 patients were treated between 1992 and 1997. Ab initio unresectability was shown by laparotomy (16 cases) or computed tomography (16 cases), and was due to vascular invasion in 27 patients, massive regional nodal metastases in nine, and both in four. The median age was 63 years (range 36-71); performance status (PS) (ECOG): 0-1 = 28 and PS 2 = 4. All the patients had measurable disease and were evaluable for response. There were seven PR (22%), 10 SD (31%), and 15 PD (47%). All of the responders underwent surgical exploration, and radical resection was possible in 5. Three of these patients are still disease-free with a follow-up of 18, 27, and 65 months; the other two cases relapsed 11 and 14 months after surgery. The median survival time was 9 months for the entire group, and 1-year survival rate was 31%. The treatment was never stopped because of toxicity. There were no CTC-NCI grade 3 or 4 toxic events; grade 1-2 diarrhea was observed in 10 cases. CONCLUSIONS: This preoperative regimen was feasible and led to a successful surgical resection in 16% of otherwise inoperable cases. The median survival was comparable with the results obtained after 5-FU infusion plus radiotherapy. The resectability rate, and the benefit in terms of survival in the resected patients, make these results worthy of confirmation by larger studies.     

Image-guided intensity-modulated radiotherapy for patients with locally advanced gastric cancer: a clinical feasibility study

Background

The aim of this study was to determine the medical and technical feasibility of intensity-modulated radiotherapy (IMRT) in high-risk nonmetastatic gastric cancer stage II and III after primary gastrectomy and D2 lymphadenectomy.

Methods and materials

A prospective nonrandomized phase II trial was performed on 25 consecutive patients with gastric cancer with high risk (T3–4, N1–3, G2–3, R0–1). The dose delivered was 45 Gy (1.80 Gy per fraction) in IMRT technique. Concurrent 5-fluorouracil-based chemotherapy at 225 mg/m² was administered as a continuous intravenous infusion. Primary endpoints were acute gastrointestinal toxicity (CTC 4.0) and technical feasibility of IMRT in regard to dose planning and radiation delivery.

Results

Early acute events were defined as clinical and chemical adverse effects of IMRT and concurrent chemotherapy during treatment. By definition, 90 days after the end of IMRT has been evaluated as acute-phase toxicity. No patient had grade 4 or higher acute adverse events. Clinical grade 3 toxicity occurred in two patients (8 %) with diarrhea and in one case (4 %) with nausea. Hematological changes with grade 3 occurred in three cases (12 %) with hemoglobin decrease, in five cases (25 %) as leukopenia, and in one case (4 %) with thrombocytopenia. The mean dose for liver was 16 Gy and the percentage volume exceeding 30 Gy (V30) was 21 %. Mean dose for right and left kidney was 9 and 13 Gy, respectively, and V20 was 9 % and 13 %, respectively. Heart received a median dose of 15 Gy and V40 was 17 %. The mean dose to the bowel was 11 Gy and V40 was 6 %. Spinal cord had at maximum 33 Gy in median. Specifics of dose distribution, including the coverage, for the target region were as follows: minimum was 33 Gy, maximum 48.6 Gy, and mean dose 44.6 Gy. The prescribed dose (45 Gy) covered 99 % and 95 % of planning target volume (OTV) in 66 % and 92 % of cases, respectively. Median PTV was 15.77 ml (range, 805–3,604 ml).

Conclusions

The data support the practical feasibility of IMRT in adjuvant treatment in high-risk gastric cancer in the postoperative setting as a proof of principle. Acute toxicity has been tolerable.     

Concurrent chemoradiotherapy combined with intraoperative radiotherapy for locally advanced pancreatic cancer: a feasibility study

Initial clinical results of concurrent chemoradiotherapy combined with high-dose intraoperative radiotherapy (IOR) for locally advanced pancreatic cancer were analyzed. Between June 1996 and May 1999, 6 patients with locally advanced pancreatic cancer without distant metastasis were treated with preoperative concurrent chemoradiotherapy followed by IOR. Preoperative radiation therapy was given by the dynamic arc conformal technique with a daily fraction of 1.8 Gy to a total dose of 45 Gy in 5 weeks. Cisplatin (5 mg/day for 4 weeks) and 5-fluorouracil (250 mg/day for 5 weeks) were administered continuously during preoperative radiation therapy. IOR as a single dose of 28 or 30 Gy was given to the gross tumor volume using electron beams of 15- to 22-MeV. Concurrent chemoradiotherapy was well tolerated, although all of the patients complained of nausea and fatigue. Two patients developed grade III leukopenia. No other serious acute toxicity was noted. The median survival time of the 6 patients was 17.5 months, which was significantly longer than that of our historical control treated with external radiation therapy with IOR (8 months), although the difference in survival was borderline significant (p=0.068). Concurrent chemoradiotherapy followed by high-dose IOR was well tolerated in patients with locally advanced pancreatic cancer, and the initial clinical results appeared promising.     

Evaluation of surgical resection in the locally advanced cervical carcinomas after neoadjuvant external beam radiation therapy

Cervical carcinomas are common in developing countries. More than 60 % of all cases are locally advanced, considered as no carcinologic resectable because of the frequent pelvic structures involvement. The aim of this study is to evaluate the surgical resection of locally advanced of the cervical carcinoma after neo-adjuvant external beam radiotherapy. It was retrospective study and we enrolled 48 cervical carcinomas staging FIGO : IIA (18,8 %), IIB (58,3 %), III (16,7 %) and IVA (6,2 %) with objective response and operated after neo-adjuvant radiotherapy from 2000 to 2003. The mean age was 48,8 years and squamous cells carcinomas represented 95,8 %. We studied surgical assessment, macroscopic residual tumour, histological evaluation and follow-up. The mean delay of the surgery was 13,2 weeks. We realized radical hysterectomy Piver's type III in 75 %, type II in 8,3 %, and extrafacial hysterectomy in 12,5 %. Pelvic lymphadenectomy was done in 26 cases. We noted 15 haemorrhages, 2 injuries of bladder and ureteri, 2 urinary fistulas and 1 radic cystitis. Two patients died of pulmonary embolism. Macroscopic residual tumour noted in 29,2 %. Of the 30 cases with histological evaluation, complete sterilization was 60 % and partial sterilization 40 %. The mean follow-up was 40 months. The rate of local control was 60,4 %. A 36 months survival was 55 % and without recurrence 92 %. Very few patients presenting locally advanced of the cervical carcinoma benefit treatment. Our results may be validate by cases control studies between patient treated by exclusive radiotherapy and patient treated by radiotherapy follow up radiotherapy of surgery.     

Benefits of external beam irradiation for peripheral arterial bypass: preliminary report on a phase I study

PURPOSE: To perform a Phase I study to determine the safety and feasibility of using external beam radiotherapy to prevent neointimal hyperplasia in patients after surgical bypass of occluded infrainguinal arteries. METHODS AND MATERIALS: All patients undergoing operative infrainguinal bypass for chronic ischemia were eligible for enrollment, although those requiring a prosthetic graft were preferentially considered. Immediately after bypass, the distal anastomosis was marked with clips, and the baseline anatomy of the anastomosis was documented with an intraoperative angiogram. The distal anastomotic site and 2 cm of surrounding tissues were irradiated to a total dose of 30 Gy, delivered in 10 fractions. The first dose was given within 48 h of surgery. RESULTS: Twenty-one patients were enrolled in this study. No anastomotic or wound problems or any other short-term complications of the treatment developed. However, at a mean follow-up of 10 months (range 3-18), 12 (57%) of the 21 grafts had occluded. Angiography was performed in 2 patients after successful thrombolysis and demonstrated normal anastomoses without residual stenosis. Evidence of stenosis at the irradiated anastomosis was seen in only 1 of the 21 patients by ongoing ultrasound surveillance. CONCLUSION: Fractionated external irradiation to a total dose of 30 Gy delivered to the distal surgical anastomosis immediately after operative bypass has no short-term complications and was associated with an apparently low rate of intimal hyperplasia. However, any possible gains made by reducing the neointimal hyperplasia at the site of anastomosis were significantly diminished by the high frequency of thrombotic events.     

局部晚期胰腺癌75 Gy同步加量放射治疗的剂量可行性研究

背景与目的：近年来,胰腺癌的发病率逐年上升,调强放射治疗(intensity-modulated radiotherapy,IMRT)已被广泛应用于胰腺癌的治疗,但多数胰腺癌IMRT的剂量学研究的处方剂量都小于60 Gy。本研究旨在探究局部晚期胰腺癌(locally advanced pancreatic cancer,LAPC)患者75 Gy同步加量放射治疗的剂量可行性并比较共面IMRT(coplanar IMRT,CO-IMRT)与非共面IMRT(non-coplanar IMRT,NC-IMRT)技术的剂量学差异。方法：纳入复旦大学附属肿瘤医院2018年1月—2021年12月收治的符合入组标准的10例接受同步加量放射治疗的LAPC患者,处方剂量为50 Gy的计划靶区(planning target volume,PTV),记为PTV_{50 Gy},处方剂量为75 Gy同步加量的PTV,记为PTV_{75 Gy},靶区照射分次均为25次。为每例患者分别设计CO-IMRT和NC-IMRT计划。同1例患者两种计划的射野数、处方剂量和危及器官(organ...     

Radical prostatectomy for locally advanced prostate cancer: results of a feasibility study (EORTC 30001)

The aim of this open, non-randomised, 2-stage feasibility study was to determine whether radical prostatectomy (RP) was safe and could provide cure for good prognosis patients with clinical T3 prostate cancer, in a multicentre setting. Cure was defined as a 3 months post-operative of undetectable serum PSA in combination with the presence of pathologically negative margins in the surgical specimen. Forty patients were enrolled of whom 38 were eligible. Six patients (5 pN+ and 1 pNx) did not meet the inclusion criteria and were excluded leaving 32 evaluable pN0 patients of whom 19 (59.4%, SE=4.26) achieved a complete response (CR) and in whom only two serious toxic events (STEs) were observed. The results of the first phase of the study passed the toxicity criteria (<3 STE's) but failed on the cure rate (>20 CRs). This resulted in discontinuation of the study after the first stage. The main reason for failure was the incidence of positive margins in the resected specimen. Although the study was stopped after the first phase, 28 of the 32 pN0 patients (87.5%) had undetectable serum PSA at 3 months. We continue to believe that RP with extensive resection can be beneficial as monotherapy for T3aN0M0 prostate cancer.     

Laparoscopic paraaortic surgical staging in locally advanced cervical cancer: a single-center experience

Background

One aim of this study was to assess the efficacy and safety of laparoscopic paraaortic lymphadenectomy for paraaortic lymph node staging in locally advanced cervical carcinoma. The second aim was to identify prognostic factors in the evolution of this disease and to evaluate how the results of the surgery modify the oncological treatment of patients.

Materials and methods

We analyzed 59 patients diagnosed with locally advanced cervical cancer International Federation of Gynecology and Obstetrics stage IB2–IVA who underwent laparoscopic paraaortic lymphadenectomy at our hospital between 2009 and 2015. Depending on the results of the paraaortic lymphadenectomy, treatment consisted of pelvic- or extended-field chemoradiotherapy.

Results

The mean age at diagnosis was 52.3 years. The median operative time was 180 min. The mean hospital stay was 1.7 days. The mean number of paraaortic lymph nodes excised was 16.4. Eight patients (13.5%) had positive paraaortic lymph nodes. Thirteen patients (22%) underwent surgery via the transperitoneal route, and 46 (78%) underwent surgery via the retroperitoneal route. The sensitivity and specificity of computerized axial tomography (CT) scanning for detecting paraaortic lymph node involvement was 75 and 86%, respectively. The statistically significant prognostic factors that affected survival were surgical paraaortic lymph node involvement, radiological pelvic lymph node involvement, and radiological tumor size as assessed with nuclear magnetic resonance. The rate of serious complications was 1.7%.

Conclusions

Pretherapeutic laparoscopic paraaortic lymphadenectomy for locally advanced cervical carcinoma allows the adaption of radiotherapy fields to avoid false-positive and false-negative imaging results.