Interstitial microwave hyperthermia combined with iridium-192 radiotherapy for recurrent tumors

From 1985 through 1987, 44 tumors in 39 patients with recurrent cancer were treated with interstitial microwave hyperthermia (HT) combined with interstitial 192Ir radiotherapy (RT). All patients had unresectable and previously treated tumors (mean RT dose 57.6 Gy). Diagnoses were squamous cell carcinoma in 27 (62%), adenocarcinoma in 11 (25%), melanoma in 5 (11%), and soft tissue sarcoma in 1 (2%) site. Interstitial RT dose was from 25 to 50 Gy (mean 38.3 Gy). The first HT session was scheduled immediately before the loading of 192Ir, and the second was scheduled following its removal. Each session lasted 45-60 min at therapeutic temperature (42.5 degrees C). Complete response (CR) was obtained in 28 (64%) sites and partial response (PR) in 15 (34%) sites. None of the CR patients had local recurrence. Tumor volume was the most important factor influencing CR (p less than 0.001). The treated site, radiation dose, and thermal dose were not significant factors for CR (p = 0.03). The overall median survival was 39 weeks, with a 2-year survival of 22%. The treatment was well tolerated, with two patients developing focal skin necrosis.     

Interstitial iridium-192 implantation for recurrent and/or locally advanced head and neck cancer

We report our experience with the use of interstitial iridium-192 implantation in the management of patients with recurrent and locally advanced squamous cell carcinoma of the head and neck. Between June 1992 and July 1998 this technique was employed in the management of two groups of patients: (1) a primary group, comprising 42 patients who had presented for the first time with advanced head and neck disease, and had therefore not undergone any previous treatment; and (2) a salvage group of 16 patients with recurrent disease previously treated with external beam radiotherapy (four received therapy to the neck, one to the cheek, eight to the tongue and three to the floor of the mouth). The follow-up in each group was short, ranging from 3 to 56 months. The overall response in the primary group was 38/42 (90%). A complete response was achieved in 35/42 (83%). In the salvage group, the overall response was 13/16 (81%); 4/16 (25%) showed a complete response and 9/16 (56%) a partial response. The estimated percentage surviving at 1 year for patients with primary disease is 70% (95% confidence interval (CI) 54–86). For those receiving salvage therapy the estimated percentage surviving at 1 year is 45% (95% CI 19–71).     

Treatment of bladder cancer with interstitial iridium-192 implantation and external beam irradiation

Although interstitial implantation of invasive carcinoma of the bladder has been shown to be an effective treatment in Europe, there has been little experience with this method in the U.S. During the past 6 years, 14 patients at the Hospital of the University of Pennsylvania with single bladder tumors less than 5 cm and no evidence of carcinoma in situ on random bladder biopsies have been treated by a combination of external beam radiation and iridium wire implant. The iridium wire is inserted by an afterloading technique following tumor exposure via suprapubic cystotomy. Following delivery of the prescribed dose, the sources are removed percutaneously. Three patients with recurrent or high grade T1 lesions and 11 patients with T2-T3A lesions have been treated. With a median follow-up of 22 months (range 17 to 65 months), 9 patients are currently NED, 4 patients have died of disease, and 1 patient has died of intercurrent disease. There have been two isolated bladder recurrences, both non-invasive, one having been treated with cystectomy and one being treated locally. In addition, one patient developed regional failure, two developed distant metastases only, and one developed local recurrence following distant failure. The 2-year actuarial local control rate is 84%, with an overall 2-year actuarial survival of 66%. Complications have been minimal. Bladder implantation by this method is technically simple and produces excellent local control with acceptable morbidity.     

Quality assurance in interstitial iridium-192 implants for breast cancer

We evaluate an easy and low cost method to decrea-sed errors in interstitial brachytherapy for breast cancer to avoid cutaneous sequelae: a simple X-ray after loading Ir-192 wires. Between January-1997 and January-1999, 575 interstitial implants of iridium-192 were performed in 572 women with breast tumors after conservative treatment. Implants evaluated were 556 (97%). Simple radiograph was made after loading iridium-192 wires into the needles to confirm the accurate positioning of radiactives sources. None errors were detected in 506 (91%) X-rays films. The errors consisted in: 33/556 (5.9%) implants with wrong position of source into the needle, 14/556 (2.5%) with wrong active or inactive length, and 3/556 (0.5%) with order confused in the implant. Systematic radiographs to check the loading of iridium-192 in interstitial brachytherapy for breast cancer represent an easy method as control of quality assurance. Correction of minimal errors was possible in all cases and it could determine a reduction of cutaneous sequelae.     

膀胱癌术后192铱腔内放疗的临床观察

目的:为减少膀胱癌术后复发,提高治疗效果。方法:采取保留膀胱术式,多次复发的表浅型膀胱癌、BCG和化疗药物灌注效果不佳者和G3或T2膀胱癌患者,共13例,术后用~(192)铱腔内近距离放射治疗,以预防复发。结果:其中8例多次复发的多发性膀胱癌放疗前3～11个月(M=8.0)复发。放疗后随方13～27个月,仅复发1例,其余7例未复发。G3或T2以上膀胱癌5例,复发2例。其他3例已随访23个月未复发。结论:膀胱癌术后腔内放疗对于预防复发具有明显效果。并对其优点、效果、副反应进行了讨论。     

High dose rate iridium-192 brachytherapy as a component of radical radiotherapy for the treatment of localised prostate cancer

AimsTo assess the treatment outcomes and toxicity of conformal high dose rate (HDR) brachytherapy boost as a means of radiation dose escalation in patients with localised prostate cancer.Materials and methodsBetween December 1998 and July 2004, 65 consecutive patients with localised prostate cancer (magnetic resonance imaging-staged T1–3 N0 M0) were treated with external beam radiation therapy (EBRT) followed by two fractions of HDR iridium-192 brachytherapy. The patients selected this treatment modality in preference to entering an ongoing randomised phase 3 trial. Any pre-treatment serum prostate-specific antigen (PSA) and Gleason score were included. The primary end point was biochemical disease-free progression. Late treatment-related morbidity was graded according to the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer criteria.ResultsThe median patient age was 67.3 years (range 47.9–80). Sixty patients (92.3%) had intermediate- to high-risk disease defined by clinical stage, presenting PSA and Gleason score/World Health Organisation (WHO) grade. With a median follow-up of 3.5 years (range 0.6–5.8), two patients had died of metastatic disease and another four patients had PSA relapse, giving a 3-year actuarial biochemical disease-free progression of 90.8%. Three patients (4.6%) had acute grade 3 genitourinary toxicity, in the form of urinary retention. Late grade 3 and 4 genitourinary toxicities occurred in four patients (6.2%) and one patient (1.5%), respectively. No late gastrointestinal toxicities were observed.ConclusionsThese results suggest that the combined modality of conformal HDR brachytherapy and EBRT is a feasible treatment modality with acceptable acute and late toxicities, comparable with those of EBRT alone. It offers an attractive conformal treatment modality with the potential of further dose escalation in the treatment of localised prostate cancer.     

Transperineal percutaneous iridium-192 interstitial template implant of the prostate: results and complications in 321 patients.

A total of 321 patients with localized adenocarcinoma of the prostate treated by modified pelvic lymphadenectomy, Iridium-192 implant, and external beam iridium radiation were retrospectively reviewed. Analysis covered 8 years between 1981 and 1989 with a median population age of 72 (range 42 through 82 years). Disease-free survival for the entire group is 69% at 5 years with a median follow-up of 34 months (range 1.5 months to 98.5 months). As expected, both bulkier disease and positive nodal status adversely affected 5-year disease-free survival (p = 0.0001 for both). For tumors stage T1b (A2), T2a (B1), T2b (B2), T3 (C) the disease-free survival is 89.5%, 89.9%, 64.7%, and 48.8%, respectively; for NO disease 5-year disease-free survival is 76.5% versus N1/N2 disease with 5-year disease-free survival of 33.2%. Local control was excellent except for bulkier disease (p = 0.009). Tumors T1b, T2a, T2b, and T3 have 60-month local control rates of 95%, 93%, 83.6%, and 73.1%, respectively. Histologic grade also affected disease-free survival and local control with grade 1, grade 2, grade 3 showing 81.2%, 65.7%, and 45.1% disease-free survival at 5 years; and 93.6%, 82.2%, and 72.4% local control at 5 years. Estimates obtained using Kaplan-Meier method. Radiation induced morbidity was analyzed separately for all patients, there were 41 patients (13% of total) with 54 documented complications. There were no Grade 4 or 5 complications as per RTOG categories. Only 3 cases showed grade 3 complications (1%) and 51 cases showed grade 2 complications (15.9%). Grade 1 complications were not recorded. Of the grade 2 and grade 3 complications 30 were GU and 22 were rectal. The morbidity associated with combined interstitial implantation by transperineal percutaneous template and external beam iridium radiation for the localized prostate cancer is minimal with excellent local control and disease-free survival.     

Interstitial brachytherapy for recurrent breast cancer using a high dose rate lr-192 remote afterloading system: a report of two cases

We employed interstitial brachytherapy using a high dose rate Ir-192 remote afterloading unit in two breast cancer patients with locoregional recurrence. In the first case, skin metastasis was treated, with favorable control of the infield tumor but subsequent persistent sequelae and multiple outfield metastases. This experience caused us to be cautious when choosing brachytherapy for the second case, in whom a solitary metastasis to an axillary lymph node was successfully treated. Although this method is still investigational, it may play a critical role in the treatment of locoregional recurrence resistant to other treatment modalities.     

Adjuvant chemotherapy in elderly patients with breast cancer: a survey of the Breast International Group (BIG).

BACKGROUND: To collect oncologists' experience and opinion on adjuvant chemotherapy in elderly breast cancer patients. MATERIALS AND METHODS: A questionnaire was circulated among the members of the Breast International Group. RESULTS: A total of 277 oncologists from 28 countries participated in the survey. Seventy years is the age cut-off commonly used to define a patient as elderly. Biological age and the biological characteristics of the tumor are the most frequently used criteria to propose adjuvant chemotherapy to an elderly patient. Combination therapy with cyclophosphamide, methotrexate and fluorouracil on days 1 and 8 is the most frequently prescribed regimen. Great interest exists in oral chemotherapy. CONCLUSION: There is interest among those who responded to the survey to validate a comprehensive geriatric assessment for use as a predictive instrument of toxicity and/or activity of anticancer therapy and to evaluate the role of a treatment option that is potentially less toxic and possibly as effective as polychemotherapy.     

Clinical results of combined treatment conformal high-dose-rate iridium-192 brachytherapy and external beam radiotherapy using staging lymphadenectomy for localized prostate cancer

PURPOSE: To report the first long-term biochemical control rate of patients treated with two protocols using a combination of external beam radiotherapy (EBRT) and high-dose-rate (HDR) brachytherapy for localized prostate cancer in Japan. METHODS AND MATERIALS: Between October 1997 and July 2001, 71 patients with localized prostatic adenocarcinoma were treated with a combination of EBRT and HDR brachytherapy. Patient age ranged from 58 to 81 years (mean 70.5). Of the 71 patients, 12, 41, and 18 had Stage T1c, T2, and T3, respectively, according to the International Union Against Cancer classification system (1997). The mean initial prostate-specific antigen (PSA) level was 24.2 ng/mL (median, 11.9 ng/mL); 30% of the patients had an initial PSA level >20 ng/mL. Of the 71 patients, 31 had received neoadjuvant hormonal therapy. Hormonal therapy before treatment was stopped at the beginning of RT in all cases. Patients in this series were treated on two protocols. In the initial protocol, patients were treated with whole pelvis EBRT to 45.0 Gy in 25 fractions and three HDR fractions of 5.5 Gy each (35 patients). In the second protocol, patients were treated with prostatic EBRT to 41.8 Gy in 19 fractions, with an added staging lymphadenectomy to rule out lymph node metastasis for patients with high-risk factors, and four HDR fractions of 5.5 Gy each (36 patients). The American Society for Therapeutic Radiology and Oncology consensus definition for biochemical failure was used. Acute and chronic toxicities were scored using the Radiation Therapy Oncology Group guidelines. Follow-up ranged from 24 to 65 months (median, 44 months). RESULTS: Of the 71 patients, 69 were alive at the last follow-up. Two patients had died of hepatocellular carcinoma and gastric cancer at 3.5 and 4.0 years after treatment with no biochemical failure. Sixty-six patients (93%), including the two who had died of intercurrent disease, showed a tendency for a PSA decline after treatment and had no biochemical or clinical evidence of disease at the last follow-up visit. Sixty patients (85%) achieved PSA nadir levels of < or =1.0 ng/mL. The biochemical/clinical failure-free control rate at 3 and at 5 years was 93% and 93%, respectively. The bladder and rectal complications were minimal. CONCLUSION: Despite the high frequency of high-risk patients in the present patient population, the actuarial biochemical control rate was 93% at 5 years. Acute and chronic toxicity with this method was acceptable. Additional long-term follow-up is required to assess this treatment, because the median survival is not likely to be reached for several years.     

Interstitial hyperthermia and interstitial iridium 192 implantation: a technique and preliminary results

A simple technique using interstitial hypertbermia in combination with interstitial Iridium 192 implantation is described in detail. This technique was initially tested on swine and later successfully tested on seven patients. The preliminary results of the City of Hope Interstitial Hyperthermia Pilot protocol are stated. The authors feel that this simple technique could be used by any radiation oncologist while performing interstitial implants in selected sites.     

Optimizing syngeneic orthotopic murine bladder cancer (MB49).

The syngeneic orthotopic murine bladder cancer model MB49 is hampered by unreliable tumor implantation. We optimized this model by a simple modification of the standard implantation technique in three groups of mice. Fifty thousand (group I), 20,000 (group II), or 10,000 (group III) tumor cells were implanted into cauterized bladders by transurethral instillation, and dwell time was prolonged to 3 h. Tumor take, survival, and bladder weights were determined as outcome variables. To verify whether this modification maintained its sensitivity to topical immunotherapy, an initial tumor load of 100,000 MB49 cells was given, and mice were treated intravesically with Bacillus Calmette-Guérin or phosphate-buffered saline. The prolonged dwell time of tumor cells resulted in take rates of 100% in all three groups. Survival and bladder weights were significantly correlated with the number of instilled cells. Even with the highest tumor load, Bacillus Calmette-Guérin therapy improved survival and reduced bladder weights significantly, as compared to PBS. Thus, the modified model is highly reliable and maintains its susceptibility to topical immunotherapy.     

Barrett's esophagus: Epidemiological and clinical results of a multicentric survey

In 1987 we established an kalian multicenter study involving 16 gastroenterologic institutions. The main aims of the study were to assess the prevalence of Barrett's esophagus in a cohort of patients undergoing upper gastrointestinal endoscopy, and the relationship between endoscopic and histologic features. We enrolled 14,898 consecutive patients, and found 251 (1.7%) had endoscopic findings consistent with Barrett's esophagus and/or esophagitis (grade 2 to 4 according to Savary). On histological examination, Barrett's esophagus was confirmed in III of 251 patients (44.2%). The crude prevalence rate of BE, based on histology, was 7.4/1000, and was 2.6-fold higher In males than In females (c.i. 1.7–4.0). Barrett's esophagus proved to be 25-fold more frequent among patients who complained of heartburn (80.1/1000) than among the others (3.2/1000). Specialized columnar epithelium was identified In 69 of 111 cases (62.2%) and the proportionate distribution of the histological subtypes was similar in males and in females (chi-square Idf = 0.20, p = n.s.). Dysplasia was detected in 7 patients, all of whom had specialized columnar epithelium (6 low grade and 1 high grade). In conclusion, we believe that our rate of 7.4/1000 approaches the true prevalence rate of Barrett's esophagus, as it is based on our study of unselected patients presenting for initial evaluation of a variety of UGI symptoms. The occurrence of dysplasia in specialized columnar epithelium suggests that patients with this subtype of Barrett's esophagus may be at increased risk for developing cancer and might, therefore, benefit most from surveillance.     

Urinary nitrate, nitrite and N-nitroso compounds in bladder cancer patients with schistosomiasis (bilharzia).

Urinary excretion of nitrite and of volatile and nonvolatile N-nitroso compounds is increased in schistosomiasis (bilharzia) patients with Schistosoma haematobium infection. This observation suggests that the formation of nitrite and N-nitroso compounds in vivo in the urinary bladder of bilharzial patients may be an important etiological factor in the induction of bladder cancer associated with S. haematobium infection.     

Self-testing for cancer: a community survey

Background  

Cancer-related self-tests are currently available to buy in pharmacies or over the internet, including tests for faecal occult blood, PSA and haematuria. Self-tests have potential benefits (e.g. convenience) but there are also potential harms (e.g. delays in seeking treatment). The extent of cancer-related self-test use in the UK is not known. This study aimed to determine the prevalence of cancer-related self-test use.     

Risk factors for delay in symptomatic presentation: a survey of cancer patients

Background:

Delay in symptomatic presentation leading to advanced stage at diagnosis may contribute to poor cancer survival. To inform public health approaches to promoting early symptomatic presentation, we aimed to identify risk factors for delay in presentation across several cancers.

Methods:

We surveyed 2371 patients with 15 cancers about nature and duration of symptoms using a postal questionnaire. We calculated relative risks for delay in presentation (time from symptom onset to first presentation >3 months) by cancer, symptoms leading to diagnosis and reasons for putting off going to the doctor, controlling for age, sex and deprivation group.

Results:

Among 1999 cancer patients reporting symptoms, 21% delayed presentation for >3 months. Delay was associated with greater socioeconomic deprivation but not age or sex. Patients with prostate (44%) and rectal cancer (37%) were most likely to delay and patients with breast cancer least likely to delay (8%). Urinary difficulties, change of bowel habit, systemic symptoms (fatigue, weight loss and loss of appetite) and skin symptoms were all common and associated with delay. Overall, patients with bleeding symptoms were no more likely to delay presentation than patients who did not have bleeding symptoms. However, within the group of patients with bleeding symptoms, there were significant differences in risk of delay by source of bleeding: 35% of patients with rectal bleeding delayed presentation, but only 9% of patients with urinary bleeding. A lump was a common symptom but not associated with delay in presentation. Twenty-eight percent had not recognised their symptoms as serious and this was associated with a doubling in risk of delay. Embarrassment, worry about what the doctor might find, being too busy to go to the doctor and worry about wasting the doctor''s time were also strong risk factors for delay, but were much less commonly reported (<6%).

Interpretation:

Approaches to promote early presentation should aim to increase awareness of the significance of cancer symptoms and should be designed to work for people of the lowest socioeconomic status. In particular, awareness that rectal bleeding is a possible symptom of cancer should be raised.     

Irinotecan is active in chemonaive patients with metastatic gastric cancer: a phase II multicentric trial

To assess the response rate and the tolerance of irinotecan as first-line therapy, 40 patients with metastatic gastric cancer received irinotecan 350 mg m(-2) every 3 weeks administered as a 30 min infusion. Among the 35 patients evaluable for response, two complete and five partial responses were recorded (response rate: 20.0% (95% CI:8.4-36.9%)). In total, 16 patients achieved stable disease and 12 progressive disease. In all, 66 percent of the patients benefited from tumour growth control. The median time to progression was 3.0 months (95% CI: 2.3-4.4%). The median overall survival was 7.1 months (95% CI: 5.2-9.0%). The probability of being alive at 6 months and 9 months was 61.0 and 32.4%, respectively. The median number of cycles per patient was 3 (range 1-14), and the relative dose intensity was 0.98. The most common grade 3-4 toxicities by patients were diarrhoea 20%, asthenia 10%, nausea 7.5%, vomiting 5.0%, abdominal pain 5%, neutropenia 38.5%, leucopenia 28.2%, anaemia 12.8% and thrombocytopenia 5.1%. Febrile neutropenia occurred in 12.5% of patients. These findings indicate that irinotecan is active and well tolerated in patients with metastatic gastric adenocarcinoma and warrants further evaluation in this clinical setting.