Iodine 125 suture implants in the management of advanced tumors in the neck attached to the carotid artery.

Between 1975 and 1982, 38 patients with locally advanced head and neck cancer attached to the carotid artery underwent surgical excision followed by iodine 125 vicryl suture implant in the neck. Most patients had neck masses that were greater than 6 cm and stage IV disease without clinically evident distant metastases. Twelve patients had received no previous therapy while 26 underwent an implant for recurrent disease. The local control rate in the implant volume was 79%. The local and regional control rate in all head and neck sites was 53%. The mean survival was 11 months. The overall complication rate was 26%. There was no significant correlation of local control or complications with the minimum total dose, volume implanted, individual 125I seed strength, or total seed strength. In patients with large masses attached to the carotid artery, surgical resection followed by a 125I implant for residual disease is a viable alternative to resection of the carotid artery.

Combined radiotherapy and chemotherapy with bleomycin and methotrexate for advanced inoperable head and neck cancer: update of a Northern California Oncology Group randomized trial.

Between 1978 and 1984, the Northern California Oncology Group (NCOG) conducted a randomized trial to study the efficacy of combined radiotherapy (RT) and chemotherapy (CT) for stage III or IV inoperable head and neck cancer. One hundred four patients were randomized to receive: (1) RT alone, or (2) RT plus CT. RT consisted of 7,000 cGy to the involved areas and 5,000 cGy to uninvolved neck at 180 cGy/fraction, five fractions/wk. CT consisted of bleomycin, 5 U intravenously (IV), twice weekly during RT, followed by bleomycin, 15 U IV, and methotrexate, 25 mg/m2 IV weekly for 16 weeks after completion of RT. Fifty-one patients in the RT alone group and 45 in the combined treatment group were evaluable. The local-regional complete response (CR) rate was 45% v 67% (P = .056); the 2-year local-regional control rate, including salvage surgery, was 26% v 64% (P = .001); and the incidence of distant metastasis was 24% v 38% (P greater than .25), for the RT alone and RT plus CT groups, respectively. The relapse-free survival curves were significantly different (P = .041), favoring the combined treatment. However, the survival curves were not significantly different (P = .16). Patient compliance to maintenance CT was poor. Bleomycin significantly increased the acute radiation mucositis, although the difference in late normal tissue toxicity was not statistically significant. Thus, bleomycin and concurrent RT produced a more favorable CR rate, local-regional control rate, and relapse-free survival, but the difference in survival was not statistically significant.

Management of breast cancer after Hodgkin's disease.

PURPOSE: To evaluate the incidence, detection, pathology, management, and prognosis of breast cancer occurring after Hodgkin's disease. PATIENTS AND METHODS: Seventy-one cases of breast cancer in 65 survivors of Hodgkin's disease were analyzed. RESULTS: The median age at diagnosis was 24.6 years for Hodgkin's disease and 42.6 years for breast cancer. The relative risk for invasive breast cancer after Hodgkin's disease was 4.7 (95% confidence interval, 3.4 to 6. 0) compared with an age-matched cohort. Cancers were detected by self-examination (63%), mammography (30%), and physician exam (7%). The histologic distribution paralleled that reported in the general population (85% ductal histology) as did other features (27% positive axillary lymph nodes, 63% positive estrogen receptors, and 25% family history). Although 87% of tumors were less than 4 cm, 95% were managed with mastectomy because of prior radiation. Two women underwent lumpectomy with breast irradiation. One of these patients developed tissue necrosis in the region of overlap with the prior mantle field. The incidence of bilateral breast cancer was 10%. Adjuvant systemic therapy was well tolerated; doxorubicin was used infrequently. Ten-year disease-specific survival was as follows: in-situ disease, 100%; stage I, 88%; stage II, 55%; stage III, 60%; and stage IV, zero. CONCLUSION: The risk of breast cancer is increased after Hodgkin's disease. Screening has been successful in detecting early-stage cancers. Pathologic features and prognosis are similar to that reported in the general population. Repeat irradiation of the breast can lead to tissue necrosis, and thus, mastectomy remains the standard of care in most cases.

Unsuspected abnormalities noted on CT treatment-planning scans obtained for breast and chest wall irradiation.

PURPOSE: Three-dimensional treatment planning and CT simulation is widely used for the treatment of a variety of cancers. At the Stanford University Medical Center, a treatment-planning CT scan is obtained before breast irradiation to optimize the dose distribution to the treated breast and to limit radiation to the opposite breast, heart, and lung. In this paper, we review the incidental findings discovered on a careful review of these scans. METHODS AND MATERIALS: Between 1997 and 1999, 153 patients referred for breast or chest wall radiation therapy underwent a treatment-planning CT scan in our department. The planning scans were extended to include not only the breast, but also the neck, thorax, and liver. A resident and attending radiation oncologist carefully reviewed each scan before approving the treatment plan. Any abnormal findings were reviewed by an attending in the department of radiology, and additional diagnostic imaging or other evaluation was obtained as necessary. RESULTS: One hundred and fifty-three sequential scans were reviewed, and 17 unsuspected abnormalities were noted (11%). The abnormalities involved the lung (n = 4), the liver (n = 3), the gallbladder (n = 4), the esophagus (n = 2), lymph nodes (n = 3), and the breast. All abnormalities were evaluated with additional imaging studies and/or appropriate consultations. Four of these abnormalities represented additional cancer foci (3%) and altered the treatment plan. CONCLUSIONS: Three-dimensional treatment-planning CT scans for breast cancer should be carefully reviewed. In our institution, 11% of these planning studies contained abnormalities, and 3% demonstrated additional unanticipated sites of involvement by breast cancer.

Radiotherapy for carcinoma-in-situ of the glottic larynx.

PURPOSE: To describe the long-term results of radiotherapy as treatment for carcinoma-in-situ of the glottic larynx. METHODS AND MATERIALS: Twenty-nine patients with a histologic diagnosis of carcinoma-in-situ (CIS) of the true vocal cord were treated in the Department of Radiation Oncology at Stanford University Medical Center over a 32-year period from 1958-1990. Twenty patients were treated at the time of initial diagnosis following biopsy only (12) or vocal cord stripping (8) and the remainder were referred for treatment of recurrent CIS following one or more prior surgical procedures. Treatment was delivered with megavoltage equipment to a total dose of 53-66.5 Gy (mean 62 Gy) in 180-250 cGy fractions. The mean follow-up time is 10 years, with a range of 2-27 years. RESULTS: Two patients relapsed locally. One patient had recurrent CIS 5 months after radiotherapy and was salvaged with vocal cord stripping. The other developed microinvasive squamous cell carcinoma and underwent total laryngectomy. The actuarial freedom from local relapse and overall survival at 10 years are 92% and 64%, respectively. No local failures occurred more than 5 years after treatment. Late complications from radiotherapy were rare, and voice quality was good-to-excellent in 90% of patients. The actuarial risk of a second aerodigestive tract malignancy is 11% at 10 years. CONCLUSION: Radiation therapy is an effective and safe treatment modality for carcinoma-in-situ of the glottic larynx. Long-term local control is achieved in approximately 90% of patients with 75% having normal voice.

Malignant obstructive jaundice: treatment with external-beam and intracavitary radiotherapy.

Eleven patients with obstructive jaundice from unresectable cholangiocarcinoma, metastatic porta hepatis adenopathy, or direct compression from a pancreatic malignancy were treated at the Stanford University Medical Center from 1978-1983 with an external drainage procedure followed by high-dose external-beam radiotherapy and by an intracavitary boost to the site of obstruction with Iridium192 (Ir192). A median dose of 5000 cGy was delivered with 4-6 Mv photons to the tumor bed and regional lymphatics in 9 patients, 1 patient received 2100 cGy to the liver in accelerated fractions because of extensive intrahepatic disease, and 1 patient received 7000 "equivalent" cGy to his pancreatic tumor bed and regional lymphatics with neon heavy particles. An Ir192 wire source later delivered a 3100-10,647 cGy boost to the site of biliary obstruction in each patient, for a mean combined dose of 10,202 cGy to a point 5 mm from the line source. Few acute complications were noted, but 3/11 patients (27%) subsequently developed upper gastrointestinal bleeding from duodenitis or frank duodenal ulceration 4 weeks, 4 months, and 7.5 months following treatment. Eight patients died--5 with local recurrence +/- distant metastasis, 2 with sepsis, and 1 with widespread systemic metastasis. Autopsies revealed no evidence of biliary tree obstruction in 3/3 patients. Mean survival time from initial laparotomy and bypass was 16.1 months, and from radiotherapy completion was 8.3 months. Evolution of radiation treatment techniques for biliary obstruction in the literature is reviewed. High-dose external-beam therapy followed by high-dose Ir192 intracavitary boost is well tolerated and provides significant palliation. Survival of these aggressively managed patients approaches that of patients with primarily resectable tumors.

125I vicryl suture implants as a surgical adjuvant in cancer of the head and neck.

Sixty-four intraoperative 125I seed implants using absorbable suture (Vicryl) carriers were performed in 53 patients with head and neck cancers at Stanford between 1975 and 1980. In previously untreated patients, local control in the implanted volume or in all head and neck sites was obtained in 79 and 71%, respectively. Five of these patients (40%) remained NED. Of 34 patients with recurrent carcinomas, local control was obtained in the implant volume in 20 (59%), while 38% had no recurrence post-implantation in any head and neck site. The incidence of complications is correlated with 125I radiation doses, total millicuries inserted, seed strength used, and tissue volume implanted for both untreated patients and those with local recurrences. Guidelines for the optimal use of the above 4 parameters are also presented. We conclude that 125I seed Vicryl intraoperative suture implants are an effective surgical adjuvant in the treatment of advanced, previously untreated or recurrent head and neck cancers.

Combined continuous ultra low dose rate irradiation and radiofrequency hyperthermia in the C3H mouse.

Intradermally inoculated RIF tumors and normal skin of male C3H mice were implanted with variable activities of Iodine 125 seeds or dummy seeds enclosed in Vicryl sutures, and subjected to 0, 1, 2 or 3 local radiofrequency heat treatments for 30 minutes. Each treatment raised the tumor volume to 44 degrees C. Gastrointestinal toxicity (assessed by weight change), skin reaction, tumor growth delay, and tumor cure were assessed. Neither radiofrequency treatment alone or continuous ultra low dose rate irradiation up to 16,000 rad over 180 days alone was successful in curing these tumors; however, combined modality treatments employing doses as low as 8,000 rad over 180 days plus two radiofrequency treatments did effect cures. Gastrointestinal toxicity was best correlated with hyperthermia treatments, while skin reactions secondary to hyperthermia were prolonged by continuous ultra low dose rate irradiation. Implications for clinical usage are discussed.

A new catheter system with remote tip guidance for endobronchial brachytherapy.

Endobronchial brachytherapy is being used with increased frequency in the treatment of recurrent neoplastic obstruction of the major airways, alone or in combination with Nd-YAG laser ablation of the occluding tumor mass. Currently available catheter systems are not reliable with respect to accurate and simple bronchoscopic guidance during placement. Flexibility, wall strength and radiation transmission characteristics are not optimized. We describe a system that meets these goals which has been designed and tested in our department. It is composed of an external handle, deflecting guidewire, and catheter specially modified for endobronchial brachytherapy, with a tip that can be maneuvered in any direction with one hand from outside the patient. Major advantages of the system are ease of concurrent bronchoscopy and catheter guidance, good dosimetric characteristics of the catheter, reasonable cost, and ready availability for adaptation to various techniques of endobronchial brachytherapy.

Radiosurgery for skull base malignancies and nasopharyngeal carcinoma.

PURPOSE: Patients with skull base lesions present a challenging management problem because of intractable symptoms and limited therapeutic options. In 1989 we began treating selected patients with skull base lesions using linac stereotactic radiosurgery. In this study the efficacy and toxicity of this therapeutic modality is investigated. METHODS AND MATERIALS: Forty-seven patients with 59 malignant skull base lesions were treated with linac radiosurgery between 1989 and 1995. Eleven patients were treated for primary nasopharyngeal carcinoma using radiosurgery as a boost (7 Gy-16 Gy, median: 12 Gy) to the nasopharynx after a course of fractionated radiotherapy (64.8-70 Gy) without chemotherapy. Another 37 patients were treated for 48 skull base metastases or local recurrences from primary head and neck cancers. Eight of these patients had 12 locally recurrent nasopharyngeal carcinoma lesions occuring 6-96 months after standard radiotherapy, including one patient with nasopharyngeal carcinoma who developed a regional relapse after radiotherapy with a stereotactic boost. Lesion volumes by CT or MRI ranged from 0 to 51 cc (median: 8 cc). Radiation doses of 7.0 Gy-35.0 Gy (median: 20.0 Gy) were delivered to recurrent lesions, usually as a single fraction. RESULTS: All 11 patients who received radiosurgery as a nasopharyngeal boost after standard fractionated radiotherapy remain locally controlled (follow-up: 2-34 months, median: 18). However, one patient required a second radiosurgical treatment for regional relapse outside the initial radiosurgery volume. Thirty-three of 48 (69%) recurrent/metastatic lesions have been locally controlled, including 7 of 12 locally recurrent nasopharyngeal lesions. Follow-up for all patients with recurrent lesions ranged from 1 to 60 months (median: 9 months). Local control did not correlate with lesion size (p = 0.80), histology (p = 0.78), or radiosurgical dose (p = 0.44). Major complications developed after 5 of 59 treatments (8.4%), including three cranial nerve palsies, one CSF leak, and one trismus. Complications were not correlated with radiosurgical volume (p = 0.20), prior skull base irradiation (p = 0.90), or radiosurgery dose > 20 Gy (p = 0.49). CONCLUSION: Stereotactic radiosurgery is a reasonable treatment modality for patients with skull base malignancies, including patients with primary and recurrent nasopharyngeal carcinoma. The dose distribution obtained with stereotactic radiosurgery provides better homogeneity than an intracavitary implant when used as a boost for nasopharyngeal lesions, especially lesions which involve areas distant to the nasopharyngeal mucosa.

Iridium-192 interstitial implant and external beam radiation therapy in the management of squamous cell carcinomas of the tonsil and soft palate.

PURPOSE: To evaluate the results, techniques, indications and complications of interstitial brachytherapy in the management of squamous cell carcinomas of the tonsil and soft palate, we reviewed the Stanford University Medical School experience with this modality. METHODS AND MATERIALS: Between May 1975 and January 1990, 37 patients with squamous cell carcinomas of the Tonsillo-Palatine region were treated with a combination of external beam irradiation and a removable Iridium-192 interstitial implant. The mean age of these patients was 56. Twenty-two were males and 15 were females. The stage distribution included four patients with Stage I, 5 with Stage II, 10 with Stage III, and 18 with Stage IV cancers. Thirty-two percent (12/37) of these patients had T3 or T4 lesions. Forty-nine percent (18/37) had stage N2 or N3 cervical lymphadenopathy. All 37 patients received initial external beam irradiation to the primary, bilateral necks, and supraclavicular region (mean dose: 5400 cGy, range 4000-6600). Eighteen patients (49%) also received neck dissections. All 37 patients received an interstitial Irridium-192 implant using a combination intraoral swage and external looping technique. The mean dose was 2700 cGy (range 2000-4000 cGy) to an average volume of 24 cc (range 5-81). RESULTS: Local control was obtained in 95% (35/37) of the patients. Eighty-seven percent (32/37) of the patients have remained disease-free in the neck. Nine patients have developed second primary lesions, and one developed pulmonary metastasis. Fifteen patients have died (6 succumbed to their cancers, 6 to second primaries, 2 to intercurrent disease, 1 from an unknown cause). The actuarial freedom from relapse is 75%, and overall survival is 64% at 5 years, with a mean follow up of 43 months (range 5-110). Complications were limited to one case of osteoradionecrosis of the mandible and one tonsillar ulcer. Functional and esthetic integrity was preserved in most of these patients. CONCLUSION: Iridium-192 interstitial implant boost combined with external beam radiation therapy is a safe and effective therapy in the management of locally advanced carcinomas of the tonsil and soft palate.

Intra-arterial infusion of radiosensitizer (BUdR) combined with hypofractionated irradiation and chemotherapy for primary treatment of osteogenic sarcoma.

Combined modality treatment was given in nine patients of osteogenic sarcoma wherein the tumor was unresectable because of location or amputation was refused. This alternative to massive surgery comprised hypofractionated irradiation, intra-arterial infusion of the radiosensitizer 5'-bromodeoxyuridine (BUdR) and adjuvant systemic chemotherapy. Local control was achieved in seven of the nine patients. Four survived, all without evidence of disease at 6, 7.1, 8.8, and 10.5 years after completion of irradiation. Pulmonary metastases developed in six patients--of whom one survives, following high-dose pulmonary irradiation and additional chemotherapy. Significant soft-tissue injury occurred in five patients. On the basis of our experience, we believe that new approaches using modifications of external beam irradiation with different fractionation schedules or better radiosensitizing compounds may hold promise for patients with non-resectable osteosarcoma.

Improved dose distribution with customized I-125 source loading in temporary interstitial implants.

I-125 sources are being used in temporary interstitial implants of various sites. Radiation safety considerations favor its use over other available radioisotopes. Cost containment is achieved by using the same sources for a number of patients. Loading I-125 seeds into implant catheters at our institutions permit customized source arrangement to optimize the implant dose patterns. Clinical examples are given for which the dose distributions achieved with customized source loading are superior to those achievable with standard Ir-192 ribbons.

Lymph node metastasis in maxillary sinus carcinoma.

PURPOSE: To evaluate the incidence and prognostic significance of lymph node metastasis in maxillary sinus carcinoma. METHODS AND MATERIALS: We reviewed the records of 97 patients treated for maxillary sinus carcinoma with radiotherapy at Stanford University and at the University of California, San Francisco between 1959 and 1996. Fifty-eight patients had squamous cell carcinoma (SCC), 4 had adenocarcinoma (ADE), 16 had undifferentiated carcinoma (UC), and 19 had adenoid cystic carcinoma (AC). Eight patients had T2, 36 had T3, and 53 had T4 tumors according to the 1997 AJCC staging system. Eleven patients had nodal involvement at diagnosis: 9 with SCC, 1 with UC, and 1 with AC. The most common sites of nodal involvement were ipsilateral level 1 and 2 lymph nodes. Thirty-six patients were treated with definitive radiotherapy alone, and 61 received a combination of surgical and radiation treatment. Thirty-six patients had neck irradiation, 25 of whom received elective neck irradiation (ENI) for N0 necks. The median follow-up for alive patients was 78 months. RESULTS: The median survival for all patients was 22 months (range: 2.4-356 months). The 5- and 10-year actuarial survivals were 34% and 31%, respectively. Ten patients relapsed in the neck, with a 5-year actuarial risk of nodal relapse of 12%. The 5-year risk of neck relapse was 14% for SCC, 25% for ADE, and 7% for both UC and ACC. The overall risk of nodal involvement at either diagnosis or on follow-up was 28% for SCC, 25% for ADE, 12% for UC, and 10% for AC. All patients with nodal involvement had T3-4, and none had T2 tumors. ENI effectively prevented nodal relapse in patients with SCC and N0 neck; the 5-year actuarial risk of nodal relapse was 20% for patients without ENI and 0% for those with elective neck therapy. There was no correlation between neck relapse and primary tumor control or tumor extension into areas containing a rich lymphatic network. The most common sites of nodal relapse were in the ipsilateral level 1-2 nodal regions (11/13). Patients with nodal relapse had a significantly higher risk of distant metastasis on both univariate (p = 0.02) and multivariate analysis (hazard ratio = 4.5, p = 0.006). The 5-year actuarial risk of distant relapse was 29% for patients with neck control versus 81% for patients with neck failure. There was also a trend for decreased survival with nodal relapse. The 5-year actuarial survival was 37% for patients with neck control and 0% for patients with neck relapse. CONCLUSION: The overall incidence of lymph node involvement at diagnosis in patients with maxillary sinus carcinoma was 9%. Following treatment, the 5-year risk of nodal relapse was 12%. SCC histology was associated with a high incidence of initial nodal involvement and nodal relapse. None of the patients presenting with SCC histology and N0 necks had nodal relapse after elective neck irradiation. Patients who had nodal relapse had a higher risk of distant metastasis and poorer survival. Therefore, our present policy is to consider elective neck irradiation in patients with T3-4 SCC of the maxillary sinus.

Stereotactic radiosurgical boost following radiotherapy in primary nasopharyngeal carcinoma: impact on local control.

PURPOSE: Treatment of patients with nasopharyngeal carcinoma using external beam radiation therapy (EBRT) alone results in significant local recurrence. Although intracavitary brachytherapy can be used as a component of management, it may be inadequate if there is extension of disease to the skull base. To improve local control, stereotactic radiosurgery was used to boost the primary tumor site following fractionated radiotherapy in patients with nasopharyngeal carcinoma. METHODS AND MATERIALS: Twenty-three consecutive patients were treated with radiosurgery following radiotherapy for nasopharyngeal carcinoma from 10/92 to 5/98. All patients had biopsy confirmation of disease prior to radiation therapy; Stage III disease (1 patient), Stage IV disease (22 patients). Fifteen patients received cisplatinum-based chemotherapy in addition to radiotherapy. Radiosurgery was delivered using a frame-based LINAC as a boost (range 7 to 15 Gy, median 12 Gy) following fractionated radiation therapy (range 64.8 to 70 Gy, median 66 Gy). RESULTS: All 23 patients (100%) receiving radiosurgery as a boost following fractionated radiation therapy are locally controlled at a mean follow-up of 21 months (range 2 to 64 months). There have been no complications of treatment caused by radiosurgery. However, eight patients (35%) have subsequently developed regional or distant metastases. CONCLUSIONS: Stereotactic radiosurgical boost following fractionated EBRT provides excellent local control in advanced stage nasopharynx cancer and should be considered for all patients with this disease. The treatment is safe and effective and may be combined with cisplatinum-based chemotherapy.

Treatment results and prognostic factors of advanced T3--4 laryngeal carcinoma: the University of California, San Francisco (UCSF) and Stanford University Hospital (SUH) experience.

PURPOSE: To review the UCSF-SUH experience in the treatment of advanced T3--4 laryngeal carcinoma and to evaluate the different factors affecting locoregional control and survival. METHODS AND MATERIALS: We reviewed the records of 223 patients treated for T3--4 squamous cell carcinoma of the larynx between October 1, 1957, and December 1, 1999. There were 187 men and 36 women, with a median age of 60 years (range, 28--85 years). The primary site was glottic in 122 and supraglottic in 101 patients. We retrospectively staged the patients according to the 1997 AJCC staging system. One hundred and twenty-seven patients had T3 lesions, and 96 had T4 lesions; 132 had N0, 29 had N1, 45 had N2, and 17 had N3 disease. The overall stage was III in 93 and IV in 130 patients. Seventy-nine patients had cartilage involvement, and 144 did not. Surgery was the primary treatment modality in 161 patients, of which 134 had postoperative radiotherapy (RT), 11 had preoperative RT, 7 had surgery followed by RT and chemotherapy (CT), and 9 had surgery alone. Forty-one patients had RT alone, and 21 had CT with RT. Locoregional control (LRC) and overall survival (OS) were estimated using the Kaplan--Meier method. Log-rank statistics were employed to identify significant prognostic factors for OS and LRC. RESULTS: The median follow-up was 41 months (range, 2--367 months) for all patients and 78 months (range, 6--332 months) for alive patients. The LRC rate was 69% at 5 years and 68% at 10 years. Eighty-four patients relapsed, of which 53 were locoregional failures. Significant prognostic factors for LRC on univariate analysis were primary site, N stage, overall stage, the lowest hemoglobin (Hgb) level during RT, and treatment modality. Favorable prognostic factors for LRC on multivariate analysis were lower N stage and primary surgery. The overall survival rate was 48% at 5 years and 34% at 10 years. Significant prognostic factors for OS on univariate analysis were: primary site, age, overall stage, T stage, N stage, lowest Hgb level during RT, and treatment modality. Favorable prognostic factors for OS on multivariate analysis were lower N stage and higher Hgb level during RT. CONCLUSION: Lower N-stage was a favorable prognostic factor for LRC and OS. Hgb levels > or = 12.5 g/dL during RT was a favorable prognostic factor for OS. Surgery was a favorable prognostic factor for LRC but did not impact on OS. Correcting the Hbg level before and during treatment should be investigated in future clinical trials as a way of improving therapeutic outcome in patients with advanced laryngeal carcinomas.

Nasopharyngeal carcinoma in the young: a combined M.D. Anderson and Stanford experience.

From 1956 to 1988, 57 children and young adults (age 4-21 years) with a diagnosis of nasopharyngeal carcinoma were treated at The University of Texas M.D. Anderson Cancer Center (42 patients) and Stanford University Medical Center (15 patients). The male to female ratio was 2:1. Forty-three patients had lymphoepithelioma, seven had undifferentiated neoplasms, and seven had squamous cell carcinoma. Two patients had Stage III disease and the remainder had Stage IV disease at the time of presentation. All patients were treated with primary radiotherapy, and 14 patients also had chemotherapy with combinations of the following drugs: dactinomycin, doxorubicin, bleomycin, cisplatin, cyclophosphamide, fluorouracil, methotrexate, and vincristine. Twenty-six patients are alive 6 to 178 months from the first day of treatment (median 93 months). The 5- and 10-year actuarial survival rates are 51% and 36%, respectively, and the corresponding disease specific survival rates were 51% and 51%. There were no recurrences after 42 months. The patterns of failure were as follows: distant metastasis only, 21 patients; locoregional metastasis only, 1; both, 5. Distant metastases most commonly occurred in bones, lungs, liver, and mediastinal lymph nodes. Chronic treatment-related morbidity was encountered in a significant number of long term survivors. Trends in the data not reaching statistical significance suggest a more favorable prognosis for a) females, b) patients less than or equal to 15 years of age, c) lymphoepithelioma or undifferentiated histologies, d) stages T3-4 NO-1 vs T1-2 N2-3 vs T3-4 N2-3, e) primary tumor dose greater than or equal to 65 Gy and f) patients who received chemotherapy.

Thermometry of interstitial hyperthermia given as an adjuvant to brachytherapy for the treatment of carcinoma of the prostate.

PURPOSE: Recurrence in the prostatic gland remains a significant problem in the management of locally advanced prostatic cancer. Transperineal thermobrachytherapy has been utilized in an attempt to improve local tumor control. The purpose of this study was to quantitate the temperature distributions obtained in carcinoma of the prostate treated with interstitial radiofrequency-induced hyperthermia given in conjunction with 192Ir brachytherapy in a Phase I study. METHODS AND MATERIALS: From 1987 until 1992, 36 patients (5 with locally recurrent, 15 with Stage B, and 16 Stage C prostate cancers) were treated with interstitial brachytherapy implants supplemented with radiofrequency-induced hyperthermia. An array of 7-32 stainless steel trocar electrodes (outer diameter = 1.5 mm, interelectrode spacing = 8 mm) were implanted into the prostate gland through a perineal approach utilizing a specially designed template. Each trocar was electrically insulated along the length which traversed surrounding normal tissues. One to three additional plastic catheters were implanted for automated temperature mapping. Thirty-four of these procedures were performed following lymph node sampling. However, the last two removable interstitial hyperthermic prostate implants were done by the transperineal route under ultrasound guidance. A hyperthermia treatment (goal of 43 degrees C for 45 minutes) was given immediately prior to the insertion and immediately following the removal of the 192Ir. A computer-controlled radiofrequency-based generator (freq. 0.5 MHz) implementing electrode multiplexing was used to induce and maintain elevated temperatures. RESULTS: Transient local pain was the most common treatment limiting factor. The average values of the measured minimum, mean, and maximum temperatures were 38.9 degrees C, 41.9 degrees C, and 45.7 degrees C in tumor, and 37.7 degrees C, 39.8 degrees C, and 42.9 degrees C in surrounding normal tissue, respectively. The percentages of mapped temperatures exceeding 41 degrees C, 42 degrees C, and 43 degrees C were 67%, 46%, and 27% in tumor, and 26%, 11%, and 4% in normal surrounding tissue, respectively. CONCLUSION: From this study we conclude that heterogeneous temperature distributions were induced in the prostate; significant normal tissue protection was realized in part through the selective insulation of sections of each electrode; and interstitial radiofrequency-induced hyperthermia of the prostate is feasible and well tolerated, with further technical developments warranted.

Interstitial 192Ir flexible catheter radiofrequency hyperthermia treatments of head and neck and recurrent pelvic carcinomas.

Since September 1983, five patients with head and neck cancers and five patients with pelvic or perineal recurrences of colorectal neoplasms received 192Ir interstitial implants through flexible afterloading catheters that were modified to allow RF hyperthermia treatments of the tumor within 1 hr pre- and post-brachytherapy. Local control in the implant volume was obtained in three of the patients with head and neck cancers (base tongue--2/4; floor of mouth--1/1) with follow-up of 9 to 42 months. Two patients had local recurrences after disease-free periods of 8 and 24 months. Two of the five patients treated for pelvic recurrences had complete responses lasting less than 3 months; prolonged stabilization (12 months) of a presacral mass in a third patient also occurred, but the neoplasm eventually regrew. Average temperatures of 39.2 degrees C to 43.7 degrees C were obtained in the implant volumes of these patients during the 45 minute heating periods which took place prior to loading, and just after removal, of the 192Ir seeds in each patient. No instances of intra or post-operative hemorrhage or necrosis of bone or soft tissues occurred in these patients. However, one individual required a permanent tracheostomy for persistent epiglottic edema after implantation as part of a base-tongue brachytherapy procedure. Interstitial RF hyperthermia in conjunction with brachytherapy appears to be a relatively safe and effective modality, but must be tested prospectively to compare its efficacy to interstitial irradiation alone.

Chemo-radiotherapy for localized pancreatic cancer: increased dose intensity and reduced acute toxicity with concomitant radiotherapy and protracted venous infusion 5-fluorouracil.

PURPOSE: Although concomitant radiation therapy (RT) and bolus 5-Fluorouracil (5-FU) have been shown to improve survival in locally confined pancreatic cancer, most patients will eventually succumb to their disease. Since 1994, we have attempted to improve efficacy by administering 5-FU as a protracted venous infusion (PVI). This study compares treatment intensity and acute toxicity of consecutive protocols of concurrent RT and 5-FU by bolus injection or PVI. METHODS AND MATERIALS: Since 1986, 74 patients with resected or locally advanced pancreatic cancer were treated with continuous course RT and concurrent 5-FU by bolus injection (n = 44) or PVI throughout the course of RT (n = 30). Dose intensity was assessed for both 5-FU and radiotherapy. Toxicity endpoints which could be reliably and objectively quantified (e.g., neutropenia, weight loss, treatment interruption) were evaluated. RESULTS: Cumulative 5-FU dose (mean = 7.2 vs. 2.5 gm/m2, p < 0.001) and weekly 5-FU dose (mean = 1.3 vs. 0.5 gm/m2/wk, p < 0.001) were significantly higher for patients receiving PVI 5-FU. Following pancreaticoduodenectomy, 95% of PVI patients maintained a RT dose intensity of > or = 900 cGy/wk, compared with 63% of those receiving bolus 5-FU (p = 0.02). No difference was seen for patients with locally advanced disease (72% vs. 76%, p = n.s.). Grade II-III neutropenia was less common for patients treated with PVI (13% vs. 34%, p = 0.05). Grade II-III thrombocytopenia was uncommon (< or = 3%) in both treatment groups. Mean percent weight loss (3.8% vs. 4.1%, p = n.s.) and weight loss > or = 5% of pre-treatment weight (21% vs. 31%, p = n.s.) were similar for PVI and bolus treatment groups, respectively. Treatment interruptions for hematologic, gastrointestinal or other acute toxicities were less common for patients receiving PVI 5-FU (10% vs. 25%, p = 0.11). CONCLUSION: Concurrent RT and 5-FU by PVI was well tolerated and permitted greater chemotherapy and radiotherapy dose intensity with reduced hematologic toxicity and fewer treatment interruptions compared with RT and bolus 5-FU. Longer follow-up will be needed to assess late effects and the impact on overall survival.