Alvaro Martinez

Combination of external beam irradiation and multiple-site perineal applicator (MUPIT) for treatment of locally advanced or recurrent prostatic, anorectal, and gynecologic malignancies

We have devised a single after-loading applicator, the Martinez Universal Perineal Interstitial Template (MUPIT), which has been used in combination with external beam irradiation to treat 104 patients with either locally advanced or recurrent malignancies of the cervix, vagina, female urethra, prostate, or anorectal region. Twenty-six patients treated for prostate cancer are excluded because of their short follow-up. Local failure developed in 13 of the 78 remaining patients (16.6%)--major complications developed in 4 patients (5.1%). Follow-up has been 1 year to 7 1/2 years; 60/78 patients have been followed for more than 2 years. All local recurrences and complications occurred before 18 months. The device consists of two acrylic cylinders, an acrylic template with an array of holes that serve as guides for trocars, and a cover plate. In use, the cylinders are placed in the vagina and/or rectum or both and then fastened to the template so that a fixed geometric relationship among the tumor volume, normal structures, and source placement is preserved throughout the course of the implantation. Appropriate computer programs have been developed to calculate the dose from these implants. The advantages of the system are (a) greater control of the placement of sources relative to the tumor volume and critical structures, as a result of the fixed geometry provided by the template and cylinders, and (b) improved dose-rate distributions obtained by means of computerized optimization of the source placement and strength during the planning phase. We conclude that the local control rate (83.4%) with low morbidity (5.1%) achieved with the combination of external beam irradiation and MUPIT applicator in these patients with locally advanced malignancies represents an improvement over previous published results with other applicators.

Analysis of failure following curative irradiation of gallbladder and extrahepatic bile duct carcinoma

Twenty patients with carcinoma of the gallbladder (GB-4 patients) or extrahepatic bile ducts (EHBD-16 patients) received radiation therapy with curative intent between January, 1980 and December, 1982. All 20 received 4500-5000 rad in 180-200 rad fractions to the tumor and regional lymph nodes. A 1000 to 1500 rad external beam boost was delivered in 180-200 rad fractions in 10 patients who received external beam alone or concomitant 5-Fluorouracil (5-FU). Three of the four GB and 5 of the 16 EHBD patients received a transcatheter boost with 192-Iridium (192Ir) to a dose of 2000-2500 rad calculated at a 0.5-0.1 cm radius. An additional 2 patients with EHBD lesions received an intraoperative electron (IORT) boost of 1500-2000 rad in one fraction calculated to the 90% isodose. Survival and patterns of failure were analyzed by site and treatment method. All four patients with GB carcinoma are dead of disease at 5 1/2, 6, 9 and 10 months from the date of diagnosis respectively. Three of the four developed diffuse peritoneal carcinomatosis. Five of the 16 patients with EHBD carcinoma are alive with a median follow-up of 18 months (range 6-23 months). Four of the 5 patients received a transcatheter 192Ir or IORT boost and all are without evidence of disease. Four of 9 patients who had a subtotal resection with transection of tumor, dilatation of the bile ducts with probes or curettement of the bile ducts developed either diffuse peritoneal carcinomatosis (3 patients) or a recurrence in the surgical scar (2 patients). Local failure was documented in 3 of the nine patients treated with external beam alone +/- 5-FU, and has been documented in one of the seven patients who received an IORT or transcatheter 192Ir boost. Further experience is necessary to determine whether this aggressive treatment will result in long-term disease-free survival in these patients.

Management of malignant airway obstruction: Clinical and dosimetric considerations using an iridium-192 afterloading technique in conjunction with the neodymium-YAG laser

Fourteen patients with malignant airway obstruction have had 21 placements of a flexible nylon catheter for afterloading Iridium-192 using the flexible fiberoptic bronchoscope. Prescribed therapy was completed in 13 patients (18 courses). All patients had prior full-dose external irradiation, and no effective surgical or chemotherapeutic options remained. While many have had a trial of neodymium-YAG (yttrium-aluminum-garnet) laser therapy alone, eight patients received laser treatment one to three weeks prior to planned brachytherapy to provide immediate relief of symptoms and/or facilitate access and safe catheter placement. Most patients (64%) had recurrent squamous cell lung cancer. A dose of 3000 cGy is currently specified to 5 mm and 10 mm in the bronchus and trachea, respectively. Nine of the 13 treated patients have had follow-up bronchoscopy at approximately three months post-treatment with improvement documented in seven and progression in two patients. One patient was clinically improved without follow-up bronchoscopy, and three patients have had insufficient follow-up. A single patient treated with laser and 6000 rad at 5 mm developed a bronchoesophageal fistula. No other complication has been observed. The technique is simple and safe with the use of laser therapy when needed and appears to offer effective palliation in most patients even when standard therapy is exhausted.

External beam and intraoperative electron irradiation for locally advanced soft tissue sarcomas

PURPOSEnIntraoperative irradiation with electrons was used in conjunction with external beam irradiation and maximal surgical resection in 20 patients with locally advanced soft tissue sarcomas or desmoids. This manuscript presents results with regard to tolerance of treatment and its impact on tumor control and survival.nnnMETHODS AND MATERIALSnTen patients presented with previously untreated primary sarcomas and 10 at the time of local recurrence (two had recurrent desmoid tumors). Tumor location was retroperitoneal in 19 and in the low anterior neck in one. A partial or gross total resection was performed prior to the external beam or intraoperative component of irradiation in every patient, but all had positive resection margins. Patients received 4500-6000 cGy of fractionated, external beam irradiation and an IORT dose of 1000-2000 cGy. Chemotherapy was given only at the time of disease progression.nnnRESULTSnFourteen of 20 patients (70%) were alive; 11 (55%) were free of disease (4/10 primary, 7/10 recurrent), but 1 required hemipelvectomy for salvage. Progression within the intraoperative irradiation field was documented in only 1 patient (5%) and within the external beam field in 3/20 (15%). Blood born distant metastasis occurred in 5 patients (25%) and peritoneal seeding in 1 (5%). The distant failure incidence by grade was 1/8 (13%) for Grades 1, 2 and 5/12 (42%) for Grades 3, 4. Only 1 patient (5%) developed a > or = severe neuropathy, and small bowel obstruction requiring exploration also occurred in a single patient.nnnCONCLUSIONnIn view of acceptable tolerance and the high current rate of local tumor control, in spite of incomplete surgical resections, further evaluation of intraoperative irradiation as a component of treatment is indicated for locally advanced primary and recurrent soft tissue sarcomas.

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.

Advanced epithelial ovarian cancer: Toxicity of whole abdominal irradiation after operation, combination chemotherapy, and reoperation

Thirty-five patients with advanced ovarian cancer have received, as salvage therapy, irradiation consisting of 30 Gy to the entire abdominal contents with partial liver/kidney shielding and boosts to 42 and 51 Gy for the paraaortic/diaphragmatic and pelvic regions, respectively. These patients had received 6 to 25 cycles (median, 11 cycles) of prior combination chemotherapy (included cisplatin in 30), with second-look laparotomy performed in 33; 24 (68%) had three or more laparotomies. Acute gastrointestinal toxicity was generally mild. Significant hematologic toxicity (leukocytes less than 2000/mm3; or platelets less than 100,000/mm3) was seen in 19 (54%); platelet suppression occurred in 18 of these 19. Nine patients failed to complete the prescribed course of therapy; in seven, this was secondary to hematologic toxicity. Amount of prior chemotherapy and advanced age correlated with degree of hematologic toxicity. Five patients without evidence of disease (laparotomy confirmed) have developed treatment-related bowel obstruction. No other chronic toxicity of clinical significance has been observed. Seven patients have developed bowel obstruction associated with progressive neoplasm. Irradiation was well tolerated symptomatically, but hematologic toxicity associated with prior chemotherapy prevented its completion in 20% of patients. Clinical manifestations of radiation bowel toxicity have been moderate to date and should be interpreted in the context of the aggressive combined modality program.

Postoperative whole abdomino-pelvic irradiation for patients with high risk endometrial cancer.

Forty-seven patients with endometrial cancer, surgical Stage I through IV, received adjuvant whole abdomino-pelvic irradiation with a nodal and vaginal boost between August 1981 through December 1986. The median age was 66.5 years (range 37-86 years). Twenty-two patients were Stages I-II, 14 Stage III, and eleven patients Stage IV. Thirty-four patients (79%) had positive peritoneal cytology, 29 patients (62%) had deep myometrial involvement, 27 patients (58%) had high grade lesions, 18 patients (40%) had either serous-papillary or adenosquamous histologic variants, and ten patients (22%) had residual disease of up to 2 cm. remaining after operation, mostly in the form of nodal disease. Twenty-four patients (51%) had two or more life time laparotomies. Mean follow-up was 40.5 mo. (range 17-85 mo.). The 5-year actuarial survival was 68% and the 5-year relapse-free survival (RFS) was 77%. The 5 year relapse-free survival for Stages I/II, III, and IV were 85%, 78%, and 53%, respectively. The 5 year relapse-free survival for grades 1/2 was 100% and for grades 3/4 was 60%. (p value of 0.0017). Acute toxicity has been modest, and particularly evident in thinner patients (weight below 115 lbs.). Chronic toxicity of significance has been limited to one patient with a conservatively managed bowel obstruction. These results are very encouraging and suggest benefit to the use of more aggressive adjuvant irradiation.

Pelvic lymphadenectomy combined with transperineal interstitial implantation of iridium-192 and external beam radiotherapy for locally advanced prostatic carcinoma: technical description

Regardless of the treatment modality, control of locally advanced extracapsular prostatic cancer remains a therapeutic challenge. At the Mayo Clinic, we have recently developed a combined approach for surgically staged patients employing interstitial irradiation with 192 Iridium via a transperineal template. The Martinez Universal Perineal Interstitial Template (MUPIT-II) and moderate doses of external beam irradiation. The procedure consists of: 1) preoperative single dose external beam irradiation to decrease potential for tumor seeding or showering of malignant cells during MUPIT-II placement; 2) adequate surgical staging through a bilateral retroperitoneal lymphadenectomy; 3) transperineal interstitial implantation of the tumor and retropubic palpation of the needles to verify proper position; 4) intraoperative X rays are taken and used for documentation of needle position as well as for calculation and optimization of the implant dose distribution with the aid of a computerized system; 5) moderate doses of external beam irradiation postoperatively to the prostate with adequate margins. Our favorable preliminary results obtained in 18 patients treated with the above approach warrant the continuation of this trial. Details of this technique are presented.

Intraoperative pterygo-palatine interstitial 125I seed implants

Abstract Intra-operative 125 I seed implants of the pterygo-palatine fossa and/or base skull region were performed in 15 patients at Stanford between 1976 and 1980. Local control was obtained in the implanted volume in 6 of the 10 previously untreated patients and in 4 of 5 of those who were treated with combined resection and seed implantation after local recurrences. The technique of base skull implantation, the low incidence of complications from this procedure and the dosimetric methods are discussed.

Acute toxicity and preliminary therapeutic results of pelvic lymphadenectomy combined with transperineal interstitial implantation of 192IR and external beam radiotherapy for locally advanced prostate cancer.

We have developed a combined modality approach for treatment of locally advanced prostate cancer consisting of: surgical staging with lymphadenectomy; transperineal placement of afterloading needles for a course of 192Ir brachytherapy; and a course of moderate-dose external beam irradiation to tight prostatic fields. The flexibility of the treatment permits adaptation of the dose to any tumor configuration. A total of 23 patients have been treated to date; 18 are available for treatment review and 14 for acute toxicity analysis. Significant morbidity has occurred in only 2 patients, 1 with a pelvic hematoma and 1 with hematoma in the wound. Local tumor response has been excellent in all but 1 patient. A good degree of symptomatic improvement was observed at the three-month follow-up. This approach appears to be safe and effective at this time. A brief review of the technique and the rationale for its use are also presented.