Irradiation with and without Razoxane in the Treatment of Incompletely Resected or Inoperable Recurrent Rectal Cancer

BACKGROUND AND PURPOSE: In an earlier phase II study, irradiation together with razoxane was shown to improve local control in recurrent rectal cancer. Therefore, the Austrian Society of Radiooncology (OGRO) initiated a randomized controlled trial in 1992 to compare this combined treatment versus radiation therapy alone. PATIENTS AND METHODS: Between 1992 and 1999, 36 patients with localized recurrences of rectal cancer were randomized to receive radiotherapy without (group A) or with razoxane (group B). The prognostic variables of the two groups were similar except for a longer median latency period from initial surgery to local recurrence in group A. High-energy photons with daily fractions between 170 and 200 cGy were used. The median total radiation dose was 60 Gy in each group. The patients in group B received a median razoxane dose of 9.6 g (range, 5-12 g). Main outcome measures were local control, overall survival, and toxicity. RESULTS: The combined treatment with razoxane increased the local control rate compared to radiotherapy alone (39% vs. 8%; p = 0.05). The median survival time was not different between the groups (20 months each). No patient in arm A but four of 18 patients in arm B survived 5 years. Acute toxic effects were of moderate degree in both groups. There were no substantial differences as to late side effects. CONCLUSION: Radiotherapy together with razoxane is superior to radiation treatment alone in recurrent rectal cancer as far as local control is concerned. In some patients, long-term survival was achieved with razoxane and radiotherapy.     

Efficacy and safety of CT-guided 125I seed implantation as a salvage treatment for locally recurrent head and neck soft tissue sarcoma after surgery and external beam radiotherapy: A 12-year study at a single institution

ObjectivesThe objective of this study was to evaluate the efficacy and safety of CT-guided radioactive ¹²⁵I seed implantation as a salvage treatment for locally recurrent head and neck soft tissue sarcoma (HNSTS) after surgery and external beam radiotherapy.Methods and MaterialsFrom December 2006 to February 2018, 25 patients with locally recurrent HNSTS after surgery and external beam radiotherapy were enrolled. All the patients successfully underwent CT-guided ¹²⁵I seed implantation. The primary end points included the objective response rate (ORR) and local progression-free survival (LPFS). The secondary end points were survival (OS) and safety profiles.ResultsAfter ¹²⁵I seed implantation, the ORR was 76.0%. The 1-, 3-, and 5-year LPFS rates were 65.6%, 34.4%, and 22.9%, respectively, with the median LPFS of 16.0 months. The 1-, 3-, and 5-year OS rates were 70.8%, 46.6%, and 34.0%, respectively, with the median OS of 28.0 months. Furthermore, univariate analyses showed that the recurrent T stage and histological grade were prognostic factors of LPFS, whereas only the histological grade was a predictor of OS. The major adverse events were skin/mucosal toxicities, which were generally of lower grade (≤Grade 2) and were well tolerated.ConclusionsRadioactive ¹²⁵I seed implantation could be an effective and safe alternative treatment for locally recurrent HNSTS after failure of surgery and radiotherapy. Recurrent T stage and histological grade were the main factors influencing the efficacy.     

Perioperative high-dose-rate brachytherapy in locally advanced and recurrent gynecologic cancer: Initial results of a phase II trial

BACKGROUND: This study was undertaken to determine the feasibility of perioperative high-dose-rate brachytherapy (PHDRB) as an adjunct to salvage surgery in primary advanced or recurrent gynecologic cancer. METHODS: Twenty-five patients with either locally advanced (n = 4) or recurrent (n = 21) gynecologic cancer suitable for salvage surgery were included. Unirradiated patients were treated with preoperative chemoradiation followed by salvage surgery and PHDRB (R0 and R1 resections receiving 16 or 24 Gy, respectively). Previously irradiated patients were treated with salvage surgery and PHDRB alone with 32 or 40 Gy for R0 or R1 resections, respectively. RESULTS: Resections were categorized as R0 in 9 patients (36.0%) and R1 in 16 (64.0%). Four previously irradiated patients suffered fatal pelvic bleeding between 8 and 13 months after surgery and PHDRB. After a median follow-up of 20 months (3-55+), the 4-year actuarial local and pelvic controls were 88.1% and 80.8%, respectively. The 4-year distant metastases-free survival was 40.9%. Four-year actuarial overall survival was 34.0%, with a median survival of 27.1 months (95% confidence interval: 17.5-36.8). CONCLUSIONS: Local and pelvic control results are excellent for this very high-risk-disease population. PHDRB dose in previously irradiated patients has been shifted to the closest lower level due to unacceptable vascular toxicity.     

Cs-131 brachytherapy for patients with recurrent glioblastoma combined with bevacizumab avoids radiation necrosis while maintaining local control

PurposeRe-irradiation of recurrent glioblastoma (GBM) may delay further recurrence but re-irradiation increases the risk of radionecrosis (RN). Salvage therapy should focus on balancing local control (LC) and toxicity. We report the results of using intraoperative Cesium-131 (Cs-131) brachytherapy for recurrent GBM in a population of patients who also received bevacizumab.Methods and MaterialsTwenty patients with recurrent GBM underwent maximally safe neurosurgical resection with Cs-131 brachytherapy between 2010 and 2015. Eighty Gy was prescribed to 0.5 cm from the surface of the resection cavity. All patients previously received adjuvant radiotherapy and temozolomide, and received bevacizumab before or after salvage brachytherapy. Seven of 20 (35%) tumors were multiply recurrent and had been previously salvaged with external beam radiotherapy. Patients received MRI scans every 2 months monitored for recurrence, progression, and RN.ResultsMedian tumor diameter was 4.65 cm (range, 1.2–6.3 cm). Median number of seeds pace was 41 (range, 20–74) with total seed activity 96.8U (range, 41.08–201.3U). At a median followup of 19 months, crude LC was 85% and median overall survival was 9 months (range, 5–26 months). There were two postoperative wound infections (10%), three seizures (15%), and 0% incidence of RN.ConclusionsOur study demonstrates that while LC and survival are similar to other studies of postoperative external beam radiotherapy, no RN occurred in any of these patients, including 7 multiply re-irradiated patients. Of interest, there were patients with multiple recurrences whose survival extended beyond 20 months. These findings suggest that the use of highly conformal Cs-131 brachytherapy is a promising treatment for patients with recurrent GBM with minimal risk of development of RN.     

High-dose-rate afterloading intraluminal brachytherapy for advanced inoperable rectal carcinoma

PurposeHigh-dose-rate (HDR) intraluminal brachytherapy for advanced or inoperable tumors of the rectum has been used both palliatively and to dose escalate after chemoradiation for curative treatment.MethodsBetween 1993 and 2007, 79 patients were treated with HDR afterloading brachytherapy for rectal cancer; 70 patients had adenocarcinoma of the rectum; and 9 patients had squamous cell carcinoma of the anal canal. Fifty-two patients had localized disease but were unfit for major surgery and received radiotherapy with radical intent. Twenty-seven patients with advanced or metastatic disease received palliative treatment. The median age was 82 years (range, 33–97). Radical treatment comprised either chemoradiation followed by intraluminal brachytherapy delivering 12 Gy at 1 cm in two fractions or radical monotherapy delivering up to 36 Gy at 1 cm in six fractions two to three times weekly. Palliative HDR brachytherapy schedules were predominantly 10 Gy at 1 cm single dose.ResultsObjective local tumor response was seen in 41 of 48 assessable patients (85%); of whom, 28 patients (58%) had a complete response and 13 (27%) had a partial response. The most common symptom was rectal bleeding, which was controlled with a complete response rate of 63%. The median duration of the symptom response was 3 months (range, 1–73), and the median survival of the palliative patients was 6 months (range, 1 week–37 months). The median survival for patients treated with radical intent was 18.5 months (range, 2–119). Six patients reported late toxicity with three cases of rectal ulcer, two strictures, and one fistula.ConclusionsIntraluminal HDR brachytherapy is effective as local treatment in both the radical and palliative setting, with high tumor and symptom response rates, and acceptable late toxicity.     

Radiotherapy with or without chemotherapy in the treatment of anal cancer: 20-year experience from a single institute

Purpose

To report the efficacy and toxicity of radio(chemo)therapy (RCT) in the management of squamous cell anal carcinoma (SQ-AC) and to evaluate the prognostic factors influencing the outcomes.

Patients and methods

A consecutive cohort of 138 patients with cT1-4, cN0-3, cM0 SQ-AC were treated with RCT between 1988 and 2011 at our department. Median follow-up time for surviving patients from the start of RCT was 98 months (range, 1–236 months). Patients were treated with a median radiation dose of 56 Gy (range, 4–61 Gy). Concurrent chemotherapy was administered to 119 patients (86%).

Results

The survival rates at 2, 5, and 10 years were 88?±?3, 82?±?4, and 59?±?6%, respectively, with a median overall survival (OS) of 167 months. The cumulative incidence for local recurrence at 2 and 5 years was 8?±?2 and 11?±?3%, respectively. The median disease-free survival (DFS) and colostomy-free survival (CFS) times were 132 and 135 months, respectively. In 19 patients (14%), a distant metastasis was diagnosed after a median time of 19 months. In the multivariate analysis, UICC (International Union Against Cancer) stage I-II, female gender, Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and good/moderate histologic differentiation (G1–2) were significantly associated with a better OS, DFS, and CFS. Conformal radiotherapy planning techniques were significantly associated with a lower cumulative incidence of local recurrence (11?±?3% vs. 38?±?19% at 5 years, p?=?0.006). A higher radiation dose beyond 54 Gy was not associated with an improvement in outcome, neither for smaller—(T1/T2) nor for larger tumors (T3/T4).

Conclusion

RCT leads to excellent outcomes—especially in patients with stage I/II and G1/G2 tumors—with acceptable toxicity. The probable advantages of high-dose radiotherapy should be considered carefully against the risk of a higher rate of toxicity. Future studies are needed to investigate the role of a more intensified (systemic) treatment for patients with unfavorable prognostic factors such as T3/T4, N+, and/or poor cell differentiation.     

Radiotherapy for patients with isolated local recurrence of primary resected pancreatic cancer

Background and purpose

To evaluate the treatment outcomes of radiotherapy and prognostic factors for recurrent pancreatic cancer.

Patients and methods

The study comprised 30 patients who developed a locoregional recurrence of primarily resected pancreatic cancer and received radiotherapy between 2000 and 2013 with a median dose of 54 Gy (range, 39–60 Gy). Concurrent chemotherapy included gemcitabine for 18 patients and S-1 for seven patients. The treatment outcomes and prognostic factors were retrospectively analyzed.

Results

The median follow-up after radiotherapy was 14.6 months. The 1-year overall survival, local control, and progression-free survival rates were 69?%, 67?%, and 32?%, respectively. The median overall survival and progression-free survival rates were 15.9 and 6.9 months, respectively. Tumor marker reduction and ≥?50?% reduction were observed in 18 and two patients, respectively. Of the seven patients who exhibited pain symptoms, four and two patients were partly and completely relieved, respectively. Late grade 3 ileus and gastroduodenal bleeding were observed in one patient each. Among the clinicopathological factors evaluated, only a disease-free interval of greater than?18.9 months exhibited a significant association with improved overall survival (p?=?0.017).

Conclusions

Radiotherapy for isolated locally recurrent pancreatic cancer resulted in encouraging local control, overall survival, and palliative effects with mild toxicity, particularly in patients with a prolonged disease-free interval. This treatment strategy should be prospectively evaluated.     

Perioperative high-dose-rate brachytherapy (PHDRB) in previously irradiated head and neck cancer: Initial results of a Phase I/II reirradiation study

BACKGROUND: This study was undertaken to determine the feasibility of salvage surgery and perioperative high-dose-rate brachytherapy (PHDRB) at the dose/fractionation schedule proposed in patients with previously irradiated, recurrent head and neck cancer or second primary tumors arising in a previously irradiated field. METHODS AND MATERIALS: Twenty-five patients were treated with surgical resection and PHDRB. The PHDRB dose was 4 Gy b.i.d. x 8 (32 Gy) for R0 resections and 4 Gy b.i.d. x 10 (40 Gy) for R1 resections. Further external beam radiotherapy or chemotherapy was not given. RESULTS: Resections were categorized as R0 (negative margins of at least 10 mm) in 3 patients (12.0%) and R1 (negative margins of less than 10 mm or microscopically positive margins) in 22 (88.0%). Twelve patients with R1 resections had microscopically positive margins (48%), and 10 patients had close margins (40%), with a median of 2.0 mm. Ten patients (40.0%) developed Radiation Therapy Oncology Group Grade 3 or greater toxicity. Seven patients (28%) presented complications requiring a major surgical procedure. Four of these complications appeared in the immediate postoperative period and were surgical in nature (flap failure, n = 2; fistula, n = 2), and the other three were mainly related to the brachytherapy procedure (n = 2) or the radiation dose delivered (n = 1). One patient died on postoperative day 11 due to bleeding. After a median followup of 14 months, the 4-year local control rate and overall survival were 85.6% and 46.4%, respectively. CONCLUSIONS: Surgical salvage and PHDRB at the dose/fractionation proposed are feasible in this high-risk population. Toxicity is high, but not substantially different from other reirradiation series. Four-year local control results are encouraging taking into account that 22 of 25 patients (88%) had either close or microscopically positive margins.     

Intraarterial 5-FU-infusion and simultaneous radiotherapy as palliative treatment of recurrent rectal cancer.

Palliative treatment of recurrent rectal cancer remains to be a challenge. From 1989 to 1991 13 patients with recurrent rectal cancer were treated with intraarterial infusion of 5-Fluorouracil and simultaneous radiotherapy in a palliative intent. Seven patients had received postoperative adjuvant radiotherapy with 56 to 60 Gy. Three patients had been treated with systemic chemotherapy. Radiotherapy of the recurrence was performed with 19.8 to 30.6 Gy in the pre-irradiated patients and with 50.4 to 59.4 Gy in the others. One complete remission, three partial remissions and nine minor responses were observed. Three patients had complete pain relief after the treatment, in the remaining patients major pain reduction was achieved. Palliation lasted from three to twelve months (median: five months). Our results indicate that locoregional chemo- and radiotherapy are a effective modality in recurrent rectal cancer.     

Reirradiation of Locally Recurrent Nasopharyngeal Carcinoma

PURPOSE: To study the efficacy of reirradiation as salvage treatment in patients with locally recurrent nasopharyngeal carcinoma. PATIENTS AND METHODS: Between 1993 and 2000, 20 consecutive patients (twelve males and eight females) with nasopharyngeal cancer, previously irradiated in different Hungarian institutions, were reirradiated for biopsy-proven locally recurrent tumor. Histologically, 85% of the patients had WHO type III, 5% type II, and 10% type I disease. Stages I-IV (AJCC 1997 staging system) were assigned to five (25%), seven (35%), five (25%), and three (15%) patients, respectively; none of them had distant metastases, and only eight (40%) displayed regional dissemination. The median time period between termination of primary treatment and local recurrence was 30 (range, 10-204) months.Brachytherapy was the method most frequently used: in ten cases alone (especially for rT1 tumors), and in eight cases in combination with external beam therapy. Two patients with locally advanced disease underwent external beam therapy only. The median dose in the event of brachytherapy alone was 20 Gy (4 x 5 Gy or 5 x 4 Gy, range, 16-36 Gy), and the dose range for exclusive external irradiation was 30-40 Gy. In cases of combined irradiation, a median 20-Gy brachytherapy (range, 16-40 Gy) was associated with 30-40 Gy of external irradiation. Radiotherapy was supplemented by neck dissection (six patients), nasopharyngectomy (one patient), or chemotherapy (eleven patients). RESULTS: 16 patients were reirradiated once, three twice, and one patient three times, with a median equivalent dose for tumor effect of 36 Gy (mean, 44 Gy; range, 19-117 Gy; the estimated alpha/beta-ratio was 10 Gy). The median equivalent dose of reirradiation for late effect on normal tissue (with an estimated 70% delivery of the tumor dose) amounted to 30 Gy (mean, 37 Gy; range, 13-101 Gy, estimated alpha/beta-ratio 3 Gy). After a median follow-up of 37 (range, 12-72) months, the overall survival was 60% (12/20). Seven of the twelve surviving patients are currently tumor-free. After primary irradiation, xerostomy occurred in all patients as an unavoidable side effect of treatment. Following reirradiation, a severe (grade 3 or higher) late toxicity (CTC criteria, version 2) has been observed in two tumor-free patients (10%) so far (necrosis of soft palate and paresis of glossopharyngeal nerve). CONCLUSION: Retreatment of nasopharyngeal carcinoma with radiotherapy (preferably a combined modality), can result in longterm local control and survival in a substantial proportion of patients, at the price of an acceptable morbidity.     

Concurrent Radiochemotherapy of Locally Recurrent or Advanced Sarcomas of the Uterus

BACKGROUND: Uterine sarcomas are rare tumors. Until now, no data on the treatment of recurrent or advanced uterine sarcomas using concurrent radiochemotherapy (RCT) has been available. PATIENTS AND METHODS: From 01/1997 to 03/2004, seven patients with locally recurrent (n = 6) or locally advanced uterine sarcomas (n = 1) received concurrent RCT after tumor surgery (R1/2 resection in 3/7 patients). A total radiation dose of 45 Gy was applied in single doses of 1.8 Gy using an external-beam technique; in addition, three to four intracavitary doses of 5 Gy were applied. Concurrent chemotherapy was generally administered as follows: 1.2 g/m(2) ifosfamide on days 1-5 and 29-33 in combination with 50 or 40 mg/m(2) adriamycin on days 2 and 30. 3/7 patients received further cycles of chemotherapy. The median follow- up was 35 months. RESULTS: All recurrences (before RCT) were localized either in the vagina or in or directly proximal to the vaginal stump. The main side effects of RCT were hemotoxicity (grade 3: n = 3/7; grade 4: n = 4/7; neutropenic fever n = 1/7) and diarrhea (grade 3: n = 5/7). At the median follow-up (35 months), 4/7 patients had recurrences (one local recurrence; one lymph node recurrence outside the irradiated field, two distant metastases). Local control in the irradiated field was 80% +/- 18% after 3 years. Disease-free survival calculated according to Kaplan-Meier was 57% +/- 19% after 3 years. Presently, 5/7 patients are still alive, corresponding to a 3-year survival rate of 83% +/- 15%. CONCLUSION: Concurrent RCT shows good local effectiveness with a good long-term survival. Further evaluation in phase II studies is recommended.     

Neutron therapy (dT, 14 MeV) for recurrence of rectal cancer: interim analysis from Münster.

For rectal recurrent cancer and macroscopic residual disease after surgery neutron radiotherapy has been suggested to be superior to photon radiotherapy. At the d,T generator in Münster (14 MeV) 20 patients have been treated with a combined photon-/neutron-radiotherapy: two patients with residual disease after surgery: among the 18 patients with rectal recurrence 15 for pain relief; all for tumor control. Tumor resection had been carried out in five recurrent tumors. Six patients presented with distant metastases. 30 to 40 Gy photons for tumor region and potential microscopic spread with 2 Gy per fraction and 5 to 10 Gy neutrons for macroscopic tumor volume with 0.7 to 1.6 Gy per fraction were applied using multiple fields (three to five). The mean follow-up period is nine months. Pain relief was achieved in eleven of 15 patients (73%), the onset of pain was fast, the probability for a pain-free period is 46% for nine months and for survival 56% for twelve months. Side-effects were slight to moderate beside a severe subcutaneous fibrosis in two patients. The superiority of neutrons to photons in rectal recurrent cancer remains questionable and is to be proven in a prospective trial comparing different schedules for frequency, onset and duration of pain relief, tumor control, survival and side-effects.     

The multimodality therapy of advanced inoperable esophageal carcinoma. A retrospective analysis]

BACKGROUND: The records of 161 patients with inoperable esophageal carcinoma were reviewed to determine the influence of concurrent radiochemotherapy and brachytherapy on overall survival. PATIENTS AND METHODS: From 1984 to 1999 161 patients suffering from advanced esophageal carcinoma Stage II to IV were treated with radiotherapy alone (131) or radiochemotherapy (30). In 48 patients additional brachytherapy was given. Median follow-up was 8 months (1 to 64 months), the median external beam doses was 51 Gy (18 to 66.6 Gy) and the median brachytherapy dose was 10 Gy (4 to 25 Gy). Chemotherapy consisted of cisplatin and 5-fluorouracil. RESULTS: Median survival for all patients was 10 months, 3-year survival rate 13% and the 5-year survival 5.2%. In univariate analysis the best results were achieved by concurrent radiochemotherapy with a median overall survival of 13 months, a 4-year survival of 18% (p = 0.0368), the combination of external radiotherapy and additional brachytherapy with a median overall survival of 14 months, a 4-year survival of 12.2% (p = 0.0008). After combination of concurrent radiochemotherapy and brachytherapy the 2-year survival rate is 58%. Multivariate analysis revealed simultaneous radiochemotherapy, external beam dose and additional brachytherapy as prognostic factors. Combination of concurrent radiochemotherapy and brachytherapy was possible without significant increase of local toxicity. CONCLUSIONS: Our retrospective analysis demonstrates that concurrent radiochemotherapy and additional brachytherapy are effective treatment schedules without significant increase of toxicity and may improve overall survival of patients with inoperable carcinoma of the esophagus. According to the results of this retrospective study, it would be appropriate to conduct a randomized trial to evaluate the benefit of combination of concurrent radiochemotherapy and brachytherapy.     

Postoperative Radiotherapy of Glioblastoma Multiforme

BACKGROUND AND PURPOSE: Different factors influence glioblastoma patients' prognosis. The aim of this retrospective, explorative analysis was to define the role of recent treatment strategies and to examine the value of different prognostic factors. PATIENTS AND METHODS: A total of 110 patients was analyzed. Complete resection, partial resection, and biopsy was accomplished in 69, 22, and 19 patients, respectively. 56 patients received conventionally fractionated radiotherapy with a median total dose of 60 Gy, 2 Gy daily. 54 patients received hyperfractionated accelerated radiotherapy with a median total dose of 54 Gy, 2 x 1.8 Gy daily. 20 patients had concomitant temozolomide (50-75 mg/m2/d), and 20 patients concomitant topotecan (0.5 mg/m2 as continuous venous infusion over 21 days). 37 patients received temozolomide as salvage therapy. RESULTS: Median overall (OS) and disease-free survival (DFS) were 8.7 and 4.8 months. After complete resection, partial resection, and biopsy, OS was 9.5, 8.5, and 5.5 months, respectively. OS was 8.5, 13.8, and 8.2 months for radiotherapy alone, concomitant temozolomide, and concomitant topotecan, respectively. Hazard ratio was 0.29 (OS; p = 0.002) and 0.32 (DFS; p = 0.003) for concomitant temozolomide compared to radiotherapy alone. Topotecan led to an increased toxicity. With 9.7 months for conventionally fractionated radiotherapy and 8.1 months for hyperfractionated radiotherapy, OS differed significantly (p = 0.003, log-rank test). OS in patients with RPA (recursive partitioning analysis) score III, IV, V, and VI was 14.1, 10, 9.5, and 5.8 months (p = 0.003, log-rank test). In the univariate (p = 0.0001, log-rank test) and multivariate analysis (p = 0.002, Cox regression), salvage temozolomide led to a statistically significant survival benefit (10.6 vs. 7.7 months). CONCLUSION: Concomitant topotecan or the use of hyperfractionated radiotherapy did not show to be superior in outcome in this retrospective analysis. Topotecan led to an increased toxicity. An attempt at complete resection is justified. Temozolomide should be integrated in therapy initially. As salvage therapy, temozolomide is also effective.     

High-dose-rate brachytherapy for previously irradiated patients with recurrent esophageal cancer

Purpose Our objective was to assess the feasibility, efficacy, and complications of high-dose-rate (HDR) brachytherapy for patients with recurrent esophageal cancer after external radiotherapy. Materials and methods Six patients with recurrent esophageal cancer after external radiotherapy were treated with HDR brachytherapy (Ir-192 source) from January 2003 to February 2004. The median age of the patients was 69 years. All patients had received external radiotherapy (median dose 60 Gy) before HDR brachytherapy. All patients underwent HDR brachytherapy once a week with a dose of 4 or 5 Gy per fraction in the esophageal mucosa (median total dose 20 Gy). The Kaplan-Meier method was used to calculate local control rates. Results The median overall survival period was 30.0 months. Local control was observed in five patients and residual tumor in one patient. Persistent local control was observed in two patients. No patient died of esophageal cancer, and all patients survived. We observed no severe late complications related to HDR brachytherapy. Conclusion These data suggest that HDR brachytherapy is an effective and safe treatment for patients with recurrent esophageal cancer after external radiotherapy.     

Favorable clinical outcomes of three-dimensional computer-optimized high-dose-rate prostate brachytherapy in the management of localized prostate cancer

PURPOSE: To report PSA relapse-free survival and toxicity outcomes of prostate cancer patients who have undergone three-dimensional computer-optimized high-dose-rate (HDR) brachytherapy with external beam radiotherapy as definitive treatment. METHODS AND MATERIALS: One hundred five patients consecutively treated between 1998 and 2004 are reported. All patients were treated with HDR boost with lr 192 (5.5-7.0 Gy), based upon postimplant CT three-dimensional treatment planning using an in-house treatment plan optimization algorithm. Three-dimensional conformal external beam radiotherapy (45-50.4 Gy) was also administered 3 weeks after the HDR procedure. Toxicity was measured using National Cancer Institutes Common Toxicity Criteria and International Prostate Symptom Score indices. RESULTS: With a median followup of 44 months (8-79 months), the 5-year PSA relapse-free survival outcomes for low, intermediate and high-risk patients were 100%, 98%, and 92%, respectively, Median urinary toxicity, and 93% of patients denied rectal problems at the time of last followup. Erectile dysfunction was noted in 47% patients at the time of last followup, but overall 80% were able to achieve vaginal penetration when those who responded to sildenafil were included. CONCLUSION: Computer-optimized three-dimensional HDR prostate brachytherapy provides excellent disease control for even high risk localized prostate cancer. Significant toxicity has been minimal.     

Neoadjuvant Radiochemotherapy in Locally Advanced Gastric Carcinoma

BACKGROUND AND PURPOSE: Gastric carcinoma is characterized by a high rate of local recurrences and distant metastases and is often not resectable due to locally advanced stage. The aim of this study was to examine feasibility and effectiveness of neoadjuvant radiochemotherapy (RCT) for locally advanced, primarily nonresectable gastric carcinoma and to achieve curative resection. PATIENTS AND METHODS: 21 patients with locally advanced gastric cancer located in cardia (n = 17) and corpus (n = 4; seven cT3; 14 cT4; 18 cN+; all cM0) with a median age of 61 years were scheduled to receive neoadjuvant RCT. Therapy consisted of a conventionally fractionated, conformal radiotherapy using the shrinking-field technique (1.8 Gy to 45 Gy + 5.4 Gy) and chemotherapy using cisplatin (20 mg/m(2), d1-5, 29-33), 5-fluorouracil (5-FU; 800 mg/m(2), d1-5, 29-33) or paclitaxel (135 mg/m(2), d1, 29). 4-6 weeks after completion of RCT, surgery was performed whenever feasible. RESULTS: Hematologic toxicity was moderate with grade 3 leukopenia in 10/21 patients and grade 3 thrombopenia in 5/21 (CTC). Nonhematologic toxicities consisted of 5/21 cases of fever as well as one fungal sepsis. Following RCT, tumors were classified resectable in 16/21 patients (76%); 12/21 patients (58%) were operated on, 11/12 achieved clear margins (R0). Response was as follows: complete remission (CR) 3/21 (14%), partial remission 13/21 (62%), no change 3/21 (14%), systemic progressive disease (PD) 2/21 (10%). The median survival and the 2-year survival rates were 18 months and 42%, respectively, for the patients following R0 resections as compared to 10 months and 0% for the remaining patients (p = 0.035). Local control (4 years) for patients following R0 resection was 89%. CONCLUSION: Neoadjuvant RCT is feasible and locally highly effective but must be further investigated involving a higher number of patients.     

Effect of radiation therapy alone or in combination with surgery and/or chemotherapy on tumor and symptom control of recurrent rectal cancer

Purpose

To define the value of radiotherapy alone or in combination with other treatment modalities in salvage and/or palliation of locally recurrent rectal cancer with or without concomitant distant metastases.

Patients and Method

A series of 280 patients, treated between 1975 and 1990 was retrospectively reviewed. The patients were divided into 2 groups: 166 patients had a local recurrence only (group 1), 114 presented with simulteneously distant metastases (group 2). In group 1, 50 patients had only radiotherapy, 20 had radiation in combination with surgery, 68 patients had radiation and chemotherapy, and 28 patients had a combination of all 3 treatment modalities. In group 2 these numbers were 41, 7, 59 and 7, respectively. The median follow-up time was 11 months (1 to 118).

Results

The 2- and 5-year survival of group 1 were 33% and 12%. In group 2 the 2-year survival was 9%. The 2- and 5-year symptom-free survival for both groups were 18%/12% and 1%/0%, respectively. There was no significant difference in survival and symptom-free survival between treatment including concomitant 5-FU or 5-FU once a week and treatment without chemotherapy. In the combined treatments which included surgery there was a longer survival and symptom-free survival. In both groups a subanalysis of the patients who had radiation only showed a dose-response relationship for symptom-free survival. This was not the case for survival.

Conclusion

In local recurrence of rectal cancer without detectable distant metastases, radiotherapy and/or surgery have value toward survival and symptom-free survival. Further intense efforts in preventing the local recurrence by improving primary treatment are warranted.     

Transperineal Low-Dose Rate Iridium-192 Interstitial Brachytherapy in Cervical Carcinoma Stage IIB

PURPOSE: To assess local control, survival and complications in patients with cervical carcinoma Stage IIB treated radically with transperineal Iridium-192 low-dose rate interstitial brachytherapy following external beam radiotherapy. PATIENTS AND METHODS: 65 women (age 25-70 years, mean 47 years) with cervical carcinoma Stage IIB were initially treated with external beam radiotherapy on a telecobalt or 6 MV linear accelerator to a dose of 50 Gy delivered in 5-6 weeks. After 2-3 weeks of completing external radiation, patients received interstitial brachytherapy with Iridium-192 (activity 0.5-1 mCi/cm) using a Syed-Neblett perineal template. The median dose delivered to the implant volume was 24 Gy (range 20-32 Gy) delivered at an average dose rate of 0.70 Gy/h (range 0.40-1.20 Gy/h). A point defined at 1.5 cm lateral to the central uterine tandem at the level of os was taken as a representative for assessing the dose to the cervix. Mean doses delivered by interstitial brachytherapy to point A, cervix, point B and rectum were 38 Gy, 34 Gy, 16 Gy and 16 Gy, respectively. RESULTS: At a median follow-up of 53 months, the actuarial disease free survival and overall survival for 65 patients at both 5 and 10 years was 64% and 44%, respectively. Response to radiotherapy was a strong predictor of local control with 82% of patients continuing to have pelvic control after initial complete response. Overall, nine (14%) patients had persistent disease, ten (15%) developed a central recurrence after initial control and three patients developed distant metastasis on follow-up. No patient had any immediate treatment-related complication. Late toxicity included grade I-II rectal reactions in five patients and grade IV bladder complication (vesico-vaginal fistula) in two patients. 5 years after treatment, one patient developed intestinal obstruction, which was relieved after conservative management. Two patients developed vaginal stenosis. The 5- and 10-year disease free survival was 48% in patients aged less than 45 years as compared to 80% in patients of more than 45 years (p = 0.009). Dose to the cervical point was a prognostic indicator with 5- and 10-year disease free survival of 47% in patients who received < 35 Gy in comparison to 80% in patients who had > 35 Gy (p = 0.03). There was no difference in local control and survival in patients with minimal and moderate parametrial involvement. Bulky disease (> 4 cm) at presentation and a longer gap between external radiation and brachytherapy showed a trend towards inferior local control. CONCLUSIONS: Interstitial brachytherapy after external beam irradiation in patients with cervical carcinoma Stage IIB results in acceptable local control, survival and complication rates. Increased dose to the cervical disease results in improved local control and survival and should therefore be considered while optimizing brachytherapy treatment plans. Comparison of the results with those of standard intracavitary therapy remains to be proven in a randomized trial.