Guy Juillard

THE ROLE OF ADJUVANT RADIOTHERAPY IN THE TREATMENT OF RESECTABLE DESMOID TUMORS

PURPOSE Desmoid tumors have a high propensity for local recurrence with surgical resection. There are many reports describing good responses of desmoid tumors to irradiation, but none have clearly established the indications for adjuvant radiotherapy in treating resectable desmoid tumors. METHODS AND MATERIALS A retrospective analysis was performed on 61 patients with resectable desmoid tumor(s) who were treated at our institution from 1965 to February of 1992. Five patients had multifocal disease and are analyzed separately. Fifty-six patients had unifocal disease, of which 34 had positive surgical margins. Forty-five of the 56 patients with unifocal disease were treated with surgery alone, while 11 were treated with surgery plus adjuvant radiotherapy. Median follow-up was 6 years. Local control was measured from the last day of treatment, and all cases were reviewed by our Department of Pathology. RESULTS Multivariate analysis of the 56 patients with unifocal disease revealed that positive margins independently predicted for local recurrence (p < or = 0.01). Only 3 of 22 patients with clear margins experienced a local recurrence, with a 6-year actuarial local control of 85%. Multivariate analysis of the 34 patients with positive margins revealed that adjuvant radiotherapy independently predicted for improved local control (p = 0.01), and patients with recurrent disease had a slightly higher risk of local recurrence (p = 0.08). The 6-year actuarial local control determined by Kaplan-Meier for patients with unifocal disease and positive margins was 32% (+/-12%) with surgery alone, and 78% (+/-14%) with surgery plus adjuvant radiotherapy (p = 0.02). Subgroup analysis of the patients with positive margins and recurrent disease revealed that those treated with surgery alone had a 6-year actuarial local control of 0% vs. 80% for those treated with surgery plus radiotherapy (p < or = 0.01). Patients with positive margins and primary disease had a trend towards improved local control with adjuvant radiotherapy, but this was not statistically significant. None of the patients treated with radiotherapy developed serious complications or a secondary malignancy. CONCLUSIONS Margin status is the most important predictor of local recurrence for patients with resectable, unifocal desmoid tumor. Adjuvant radiotherapy is indicated in the treatment of patients with positive margins following wide excision of recurrent disease. The role of adjuvant radiotherapy in patients with positive margins following resection of primary disease is controversial, and should be based on a balanced discussion of the potential morbidity from radiotherapy compared to the potential morbidity of another local recurrence. Adjuvant radiotherapy is less likely to benefit those with clear margins due to the excellent results for these patients treated with surgery alone. The local control of desmoid tumor in the adjuvant setting is excellent with total doses ranging from 50-60 Gy, with acceptable morbidity. Field sizes should be generous to prevent marginal recurrences, and large volume MRIs of patients with extremity lesions should be used to identify those patients with multifocal disease.

Mucosal melanoma of the head and neck: The impact of local control on survival

The management for mucosal melanoma of the head and neck is controversial in view of the poor prognosis. Thirty‐five patients seen from 1955 to 1991 were analyzed retrospectively. Almost all (34/35) presented with localized disease. Primary treatments included radical surgery (15), local resection (11), radiation therapy (6), or systemic treatment (2). While the rate of local recurrence was high (27/34), only 5 patients developed distant disease before local relapse. Furthermore, only 5/21 achieved successful local salvage. Patients with their disease controlled locally had significantly longer survival than those with persistent local disease (P = .0001). The 5‐year disease‐specific survival was 45%.

Positron emission tomography with fluorodeoxyglucose to evaluate tumor response and control after radiation therapy

PURPOSE Following radiation therapy, evaluation of viable tumor can often be difficult with anatomic imaging criteria (tumor size alone). In this study, the utility of biochemical imaging with the glucose analog 2-[F-18]fluoro-2-deoxy-D-glucose and positron emission tomography was investigated in patients treated with radiation therapy. METHODS AND MATERIALS Between 1990 and 1992, 19 patients were studied, including 15 patients with head and neck cancer, (4 oropharynx, 4 sinus, 3 larynx, 2 hypopharynx, 2 oral cavity [one patient], 1 nasopharynx), and 4 patients with breast cancer. Post-radiation positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose studies were done in all patients, with 9 head and neck patients receiving pre-radiation positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose scans as well. Results were correlated with other imaging techniques and pathology. RESULTS Positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose detected head and neck primary tumors and lymph node metastases in all nine pre-radiation scans, while magnetic resonance imaging failed to detect two primary tumors. Serial positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose showed a significant decrease in tumor activity after radiation therapy, compared to pre-radiation levels, (p < 0.05), except for two patients with increased uptake at the primary site. Biopsies of these two patients showed persistent/recurrent disease after radiation therapy, which was not detected by magnetic resonance imaging. Six additional head and neck patients, with suspicious examination and inconclusive magnetic resonance imaging, were imaged with positron emission tomography after radiation therapy only. Five patients had increased positron emission tomography activity, with corresponding biopsies positive in four patients, and negative in one patient with clinically worsening symptoms. The remaining sixth patient had minimal and stable positron emission tomography uptake, and is improving clinically. Four patients had mammogram findings suspicious for recurrence after conservation treatment for breast cancer. Positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose showed no focal activity in the breast in two patients, and increased activity in the area suspicious for recurrence in the other two patients. Biopsies correlated with positron emission tomography results. CONCLUSION Changes and presence of positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose activity correlated with pathologic findings in head and neck and breast cancer patients in this series. In patients with elevated or rising positron emission tomography activity after radiation therapy, persistent or recurrent disease was found in 89% of patients, (8/9). Magnetic resonance imaging did not detect the head and neck recurrences, and mammography was suspicious in patients with both benign and malignant breast changes after radiation therapy. In addition, our data indicate that in head and neck patients with pre-radiation positron emission tomography scans, a significant decrease in activity should occur after radiation therapy, if local control is to be expected.

Accuracy and clinical impact of mediastinal lymph node staging with FDG-PET imaging in potentially resectable lung cancer.

To determine the sensitivity, specificity, and accuracy of staging mediastinal nodal disease in potentially resectable lung cancer using fluorodeoxyglucose-positron emission tomography (FDG-PET), computed tomography (CT), or both and compare these results to surgical staging. We also assessed whether PET scanning results changed clinical management. From 1992 to 1997, 50 patients underwent CT, and PET scanning before or close to the time of surgical staging. Sensitivity, specificity, accuracy, and predictive values were then calculated based on pathology results. A retrospective review of the records was performed to determine how PET results affected clinical treatment decisions. Forty-seven of 50 patients had non-small-cell lung cancer. The prevalence of pathologically confirmed mediastinal and hilar involvement was 38%. The sensitivity, specificity, and accuracy of mediastinal disease staging were as follows: CT alone = 73%, 77%, 76%; PET alone = 73%, 94%, 87%; PET + CT = 82%, 96%, 91%, respectively. PET was more specific and accurate than CT (p = 0.025). The results of PET changed management decisions in 12 of 50 cases (24%). Using FDG-PET in conjunction with CT scanning provides the most accurate staging of mediastinal disease in lung cancer by contributing complementary information. Furthermore, PET can affect clinical decision-making and allow some patients considered unresectable a chance for resection.

Concomitant pilocarpine during head and neck irradiation is associated with decreased posttreatment xerostomia

PURPOSE To retrospectively compare subjective postirradiation xerostomia scores of patients who received concomitant oral pilocarpine during radiotherapy for head and neck cancer and 3 months thereafter with those of similar cohorts who did not receive pilocarpine. METHODS AND MATERIALS Subjective xerostomia was assessed using a visual analog scale xerostomia questionnaire that measured oral dryness, oral comfort, difficulty with sleep, speech, and eating. The concomitant pilocarpine group had both parotid glands in the initial field treated to at least 45 Gy and received 5 mg pilocarpine hydrochloride four times per day (q.i.d.) beginning on the first day of radiotherapy and continuing for 3 months after completion of radiation. The control cohort had also received at least 45 Gy to both parotid glands and had not received pilocarpine at the time of evaluation. Scores on the visual analog scale were averaged and compared using the Students t-test. RESULTS Seventeen patients who received concomitant pilocarpine during head and neck irradiation and 18 patients who had not been treated with pilocarpine were available for follow-up. The mean intervals between completion of radiation and evaluation of xerostomia were 17 months and 16 months, respectively. Only one of the pilocarpine-treated patients was still taking pilocarpine at the time of evaluation. For each of the individual components of xerostomia scored on the visual analog scale, as well as the composite of all components, the group that had received oral pilocarpine during radiation had significantly less xerostomia (p < 0.01 for each). CONCLUSIONS The use of 5 mg oral pilocarpine q.i.d. during radiotherapy for head and neck cancer and 3 months thereafter was associated with significantly less subjective xerostomia than that reported by a similar cohort of patients who had not received pilocarpine. The continued use of pilocarpine does not appear to be necessary to maintain this benefit in most patients.

Preoperative radiation therapy for locally advanced vulvar cancer

Eight patients with locally advanced vulvar cancer that would have necessitated pelvic exenteration to encompass the primary tumor were given preoperative radiation therapy in an attempt to shrink the primary tumor and allow more conservative surgery. From 4400 to 5400 rad of external radiation were delivered to the primary tumor, and one patient received an additional 2400 rad from intracavitary therapy. Satisfactory shrinkage of tumor occurred in seven of the eight patients (87.5%), thus allowing conservative surgical excision. In four patients (50%), there was no viable tumor in the surgical specimen. Moist desquamation of the vulva occurred in all patients and was of sufficient severity to require temporary cessation of radiation in four patients (50%). Five received groin radiation, and one (20%) subsequently developed bilateral hip fractures. No other major morbidity occurred. Five of the eight patients (62.5%) are alive without evidence of disease at intervals ranging from 15 months to 10 years. Preoperative radiation in this group obviated the need for pelvic exenteration, resulting in significantly less morbidity without compromising survival.

Nasopharyngeal carcinoma: Treatment results with primary radiation therapy

One hundred three patients with nasopharyngeal carcinoma were treated with radiotherapy at UCLA Medical Center from January 1955 to December 1990. Overall survival, disease‐free survival, and local control rates were analyzed. In addition, survival from 1955 to 1978 and from 1979 to 1990 were evaluated. Overall 5‐ and 10‐year actuarial survival rates for all patients were 58% and 47%, respectively. Disease‐free survival rates at 3 and 5 years were 45% and 30%, respectively. Local, persistent, or recurrent disease in the nasopharynx was the primary cause of failure, occurring in 32% of patients and correlating with the initial tumor size (T stage). Twenty‐four percent of patients developed distant metastases, which correlated with nodal status but not with T stage. Seventy‐nine percent of patients failed either locally or distally by 4 years. Sex, race, age, and T and N stage categories were evaluated as prognostic variables in terms of survival. Control of primary disease is important in determining long‐term outcome. Modern imaging techniques have greatly assisted in the evaluation of disease extent and treatment options.

Concurrent cisplatin and 5-fluorouracil chemotherapy and radiation therapy for advanced-stage squamous carcinoma of the vulva

Abstract A phase II trial of concurrent cisplatin and 5-fluorourcacil (5-FU) chemotherapy and radiation therapy (CT + RT) was conducted for the primary treatment of 12 patients with retrospective surgical FIGO stages III–IV squamous carcinoma of the vulva. Eight patients were stage III and four were stage IV. Chemotherapy was used as a radiation sensitizer and it was administered in two 5-day cycles 28 days apart. Cisplatin, 50 mg/m 2 /day iv on Days 1 and 2 or 100 mg/m 2 on Day 1 or 2, plus continuous-infusion 5-FU, 1000 mg/m 2 /day for 4–5 days commencing on Days 1 and 28 of external-beam radiation therapy, are given. The pelvic radiation to a dose of 4400–5400 cGy is administered AP and PA to treat the primary tumor, the groin nodes, and the iliac vessels to the level below the common iliac nodes. Complete tumor responses were seen in 8 of 12 (67%) patients. Responses were observed in 6 of 8 (75%) stage III patients and 2 of 4 (50%) stage IV patients. Partial response were observed in 3 patients, and 1 patient had persistent disease. At the completion of concurrent chemoradiation therapy, radical vulvectomy or excision was used in 3 patients and posterior exenteration in 1. With a median follow-up of 37 months (range, 7–60 months), 10 patients are alive and free of disease, and 2 patients died at 12 and 15 months. There were no treatment-related deaths and no grade 4 toxicity. The morbidity included moist desquamation of the vulva in all patients, with grade 2 toxicity in 10 and grade 3 in 2. One patient had a deep venous thrombosis that responded to anti-coagulation therapy. These data support the use of concurrent cisplatin and 5-FU chemotherapy and radiation therapy as an alternative to primary radical surgery to treat advanced-stage squamous carcinoma of the vulva.

Radiation tolerance of transverse rectus abdominis myocutaneous-free flaps used in immediate breast reconstruction

The authors determine the effects of postoperative radiation therapy on flap and local control outcomes in patients who have undergone immediate transverse rectus abdominis myocutaneous (TRAM)-free flap reconstruction after modified radical mastectomy for locally advanced breast cancer. Details of surgery, chemotherapy, and radiation therapy for 21 patients who had undergone immediate TRAM-free flap reconstruction after modified radical mastectomy were gathered retrospectively. The outcomes examined were flap complications, overall cosmesis, and local recurrence rate. Radiation therapy was indicated for large primary tumors (T3-T4), close or positive margins, or extensive nodal disease. With a mean follow-up interval of 19 months, there have been no flap complications or losses. Cosmesis was rated as excellent by 60% of patients, good by 30%, and fair by the remaining 10%. Three patients thought that radiation had improved cosmesis, one noted worse cosmesis, and the remainder thought it had no effect on cosmesis. The local control rate was 86%. Postreconstruction irradiation of TRAM-free flaps used in immediate reconstruction for locally advanced breast cancer appears safe and cosmetically acceptable.

Major salivary gland tumors: Treatment results and prognostic factors†

A retrospective review of 133 patients with major salivary gland carcinomas treated between 1955 and 1981 is presented. The majority of cases (104) originated in the parotid gland. The most common histological type was mucoepidermoid carcinoma (39 cases). Tumor‐free interval was longest for patients with acinic cell and mucoepidermoid carcinomas. In contrast, adenoid cystic carcinoma was poorly controlled, regardless of the form of treatment.