Postoperative irradiation for squamous cell carcinoma of the head and neck.
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Biomedical subjects
Publications and source records attributed to B Vikram.
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We reviewed the records of 104 patients with Stage T1NO or Stage T2NO epidermoid carcinoma of the supraglottic larynx treated between 1965 and 1979. In 79 patients, surgery was the only type of initial treatment. These 79 patients are the subjects of this report. Forty-eight (61%) of these patients were treated by total laryngectomy, whereas 31 (39%) had a partial laryngectomy. An elective unilateral radical neck dissection was performed on 31 patients considered at high risk, but metastatic disease was found in the dissected side of the neck histologically in only 32% (ten of 31) of these patients. The minimum follow-up period was 5 years and the maximum was 20 years. Twenty-nine percent of the patients (23 of 79) experienced a neck relapse. The neck relapse rate was the same whether the patients did or did not have an elective radical neck dissection. Among the patients who experienced a neck relapse, 65% (15 of 32) have died of the cancer. Among those who did not experience a neck relapse, none (zero of 56) have died of the cancer (P less than 0.01). These results indicate that in surgically treated patients with early stage supraglottic larynx cancer, neck relapse was the major cause of failure associated with death from cancer. Strategies for decreasing the relapse rate are discussed.
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Cisplatin-based chemotherapy has yielded high response rates in patients with head and neck cancer but has failed to improve the survival rates in randomized studies. Thus, its place in the management of head and neck cancer remains unclear. We have been investigating whether the combination of chemotherapy and radical irradiation as an alternative to morbid surgery in selected patients might yield an improved quality of life without compromising survival. Between January 1983 and December 1985, we treated 32 patients with epidermoid carcinoma arising from the larynx, base of the tongue, or hypopharynx, using an interdisciplinary regimen, with the objective of avoiding total laryngectomy. All of these patients had large primary tumors that could not have been removed without total laryngectomy. Patients who could be treated by conservation laryngeal surgery were excluded, as were patients who presented with clearly unresectable disease. The regimen employed cisplatin-based chemotherapy together with brachytherapy and external radiation therapy, with highly individualized treatment planning. Seven patients had T2 lesions, 19 had T3, and 6 had T4. The follow-up periods ranged from 8 to 38 months (median, 18). The actuarial survival rate at 2 years is 85%, and the laryngectomy-free rate at 2 years is also 85%. None of the 11 patients with laryngeal cancer has relapsed, and none has required laryngectomy. None of the 12 patients with base of the tongue cancer treated by brachytherapy has relapsed above the clavicles and none has required laryngectomy, but 1 patient has died of complications of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
We reviewed the records of patients with Stage I and II epidermoid carcinoma of the supraglottic larynx treated at the Memorial Sloan-Kettering Cancer Center (MSKCC), New York, and at the Rotterdam Radio-Therapeutic Institute (RRTI), The Netherlands, between 1965 and 1979. At the MSKCC the treatment modality of choice for the primary tumor as well as for the neck had been surgery; of the 79 patients treated by surgery an elective neck dissection was performed on 31 patients. At the RRTI, however, the initial treatment for the primary tumor and the neck is radiation therapy. One-hundred and one patients were treated of whom 79% (80/101) had radiation therapy to the primary tumor as well as to both sides of the neck. This paper focuses on the problem of relapse in the neck, thus comparing patients treated in two large cancer centers by different treatment philosophies, that is elective neck dissection on one side of the neck versus elective radiation therapy to both sides of the neck. Twenty-nine percent of the patients from MSKCC (23/79) relapsed in the neck. The relapse rate was identical between the patients who did not have an elective radical neck dissection, and those who did. Among the patients who relapsed in the neck 65% (15/23) have died of the cancer, while among those who did not, none has died of supraglottic larynx cancer. Twenty-three percent (23/101) of the patients of the RRTI relapsed in the neck. Those who received radiation therapy to the primary tumor only relapsed regionally in 38% (8/21); treatment of both sides of the neck reduced the incidence of nodal recurrence to 19% (15/80). The majority of patients who relapsed in the neck eventually died of the cancer, that is 57% (13/23). Data from both institutions once again demonstrate the impact on survival of a relapse in the neck. Best strategies for decreasing the relapse rate in the neck are discussed; the conclusion was reached that, so far, elective radiation to both sides of the neck is the preferable treatment.
Methods for selecting and computing arbitrary image sections for displaying anatomic and isodose information for three-dimensional treatment planning are investigated. Selection of the desired plane may be made by defining a plane that is perpendicular to an existing image section (called the base image) and passing through a line on the base image. Alternatively, the anatomic structures displayed perspectively in three dimensions as a series of contours that can be rotated and translated may be used to define an arbitrary plane for image reconstruction. The viewing screen is considered to be the plane of interest. As a typical three-dimensional image of 30 to 60 sections requires considerable computer storage (on the order of 25 megabytes), a reconstruction algorithm may need extensive memory space or CPU and disk I/O time. Of the schemes examined, we believe the following is the most efficient. One pair of images is read from the disk at a time in sequence and intersections of the rows of the cutting plane with the box formed by the consecutive images are computed. Pixel values of all points between the given images are computed by interpolation. Special cases, such as the cutting plane being parallel to or coincident with an existing image, must be considered separately.
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Fifty-one patients with locally advanced squamous cancer of the head and neck (SCHN) were treated with up to three cycles of very-high-dose cisplatin, 187.5 mg/m2 (administered over five days) in hypertonic saline, and bleomycin infusion, 60 U/m2 (administered over five days), prior to definitive local therapy, in an attempt to improve complete remission (CR) and overall response rates. After chemotherapy, patients underwent surgery if the tumor was resectable for cure, (unless the operation involved total laryngectomy), and/or locoregional radiation therapy. Twelve patients (24%) achieved CR and 23 (45%) partial remission (PR) for an overall response rate of 69%. Thirty-nine of the 51 patients are evaluable following chemotherapy and locoregional treatment, and 28 (72%) have achieved disease-free status. Seven of these 28 (25%) have subsequently relapsed. Eleven of the 51 patients (22%) have died at median follow-up of 10+ months (3+ to 24+). Nausea and vomiting (94%) was the most severe acute toxicity. Myelosuppression was mild and nephrotoxicity was effectively prevented by the 3% saline diuresis. Bleomycin was withheld in 12 of 49 (24%) because of deterioration in pulmonary function tests. Ototoxicity in 12 of 49 (25%) and neurotoxicity in 19 of 49 (39%) were the most significant long-term toxicities. Very-high-dose cisplatin and bleomycin in this study was an effective chemotherapy regimen, but not more so than more conventional doses of cisplatin. Toxicity from both drugs was significant.
Twenty patients with Stage IV and five patients with Stage III carcinoma of the head and neck were treated with the combination of cisplatin and vinblastine before locoregional therapy. Among 24 patients evaluable for response after chemotherapy, there were four complete responders and 16 partial responders for an overall major response rate of 83%. No complete responses were observed in patients with T4 primary lesions or N3a nodal disease. Toxicity was limited primarily to nausea and vomiting (76%) and myelosuppression (72%). Four patients, all treated at the higher vinblastine dose, required hospitalization for fever associated with neutropenia. Two patients had a transient increase in the serum creatinine clearance to greater than 3 mg/dl. The combination of high-dose cisplatin and frequent vinblastine has significant activity in locally advanced squamous cell carcinoma of the head and neck, has mild and reversible toxicity, and does not require prolonged hospitalizations for continuous intravenous infusions.
Patients with head and neck cancer who have a relapse of the disease above the clavicles can sometimes be salvaged by additional surgery. However, if all gross tumor cannot be removed during surgery or if the resection margins are unsatisfactory, the likelihood of salvage is remote, especially when postoperative radiotherapy is not feasible due to previous radiotherapy. Between 1979 and 1983, we employed intraoperative brachytherapy for 21 such patients. Sixteen patients had a recurrence after previous surgery and radiotherapy, and 5 after radical radiotherapy. All gross tumor could not be removed in 15 patients, whereas satisfactory margins could not be obtained in 6. In 11 patients, we delivered radiotherapy by a temporary implant of iridium-192 (median dose 4,800 rads in 6 days). In 10 patients, radiotherapy was delivered by a permanent implant of iodine-125 (median activity 13 mCi). Three patients (14 percent) had a relapse within the surgical field, whereas six others (28 percent) had a relapse elsewhere or had development of metastases. Complications developed in four patients (19 percent) and were fatal in one patient. The actuarial disease-free survival rate at 2 years was 55 percent, whereas the rate of local disease control was 81 percent. Our experience suggests that intraoperative brachytherapy can salvage certain high-risk patients with head and neck cancer.
The results of treatment in the first 20 patients treated by a non-looping afterloading technique for base of tongue implant are described. Ten patients had carcinoma recurrent in the base of tongue after previous treatment and they were treated by implant alone. The other 10 patients had previously untreated carcinoma of the base of tongue and they were treated with a combination of interstitial implant, external radiation therapy and surgery. The minimum follow-up is 1 year and maximum 5 years. No local or regional failures have occurred in the previously untreated patients. No local failures have occurred in the previously treated patients who had lesions up to 4 cm in diameter, but three out of four patients with recurrent lesions larger than 4 cm have failed locally. Two patients developed necrosis related to the implant; the factors responsible for this are discussed.
Between 1970 and 1980, we treated 107 previously untreated patients with biopsy proven carcinoma of the nasopharynx by megavoltage external radiation therapy to the primary site, base of the skull and both sides of the neck. Fifty-three percent of the patients had T4 primaries and 87% had Stage IV disease. The histology was poorly differentiated, undifferentiated or anaplastic carcinoma in 81% of the patients, and well differentiated or moderately well differentiated epidermoid carcinoma in 19%. The dose of irradiation to the primary site ranged from 5700 to 7700 rad. Fifty-five patients have suffered relapse of the cancer, 33 of whom (60%) relapsed at the primary site. Seventy-two percent of the relapses at the primary site appeared within two years after treatment and 91 percent within 3 years. Median survival following relapse at the primary site was 10 months. Those patients who received a dose to the primary between 5700 and 6700 rad had a lower rate of local control than those who received a dose between 6700 and 7700 rad. However, regardless of the dose, those patients whose radiation therapy was interrupted (for whatever reason) for a total of three weeks or longer had poorer local control than those patients whose treatment was not so interrupted. The highest rate of local control (84%) was observed in those patients who did not have such interruptions and received a dose of 6700-7700 rad to the primary. Improved local control with the higher doses was especially striking for T4 primaries, suggesting a dose-response relationship. The local control rate did not appear to be significantly influenced by age, sex, birthplace or histology. These data suggest that a high rate of local control is possible in carcinoma of the nasopharynx, even with T4 disease, if a sufficiently high dose of radiation therapy is delivered without undue interruptions.
To improve the quality of patient care by detecting and preventing many types of treatment mistakes, we have implemented a computerized system for recording and verifying external beam radiation treatments on our therapy machines. It inhibits the radiation beam if treatment machine settings do not agree with prescribed values to within maximum permissible deviations (tolerances). The tolerances are determined from experience and adjusted when necessary to make the system more effective and less susceptible to "false alarms." The system uses a common data base for all treatment machines. As a result, it permits statistical analysis and generation of reports based on data encompassing the entire patient population as well as verification of treatments of patients transferred from one machine to another. Reports of verification failures reveal patterns of mistakes. Knowing these, attempts can be made to reduce the frequency of verification failures. "Significant" mistakes that were prevented are extracted by treatment planning personnel from these reports. Analysis of data indicates a rate of approximately 150 "significant" mistakes detected and prevented per machine per year, representing 1.0% of all fields treated. We present and discuss our experiences with the system and with the frequency, patterns, and significance of verification failures. We selected a few of the patients for whose treatments significant set-up mistakes were made, and were detected and prevented by the Record and Verify System. We include discussions of the overall effect these mistakes would have had on dose distribution had they not been prevented.
This comparison of tube feeding with oral nutrition was made in patients with advanced head and neck cancer during intensive outpatient radiation therapy. Twenty-six patients with Stage III and IV head and neck cancers were stratified by site (nasopharynx vs. all other tumors, including recurrent nasopharynx) and randomized to receive oral or tube feeding during radiation therapy. All patients were counseled to have an intake of 40 kcal/kg and 1 gm protein per kilogram body weight. Body weights and dietary recalls were obtained weekly, along with evaluation of toxicities to therapy. Serum albumins were obtained at baseline, week 4, end of radiation therapy, and 1 month after radiation therapy. Patients with nasopharyngeal carcinoma presented with significantly less body weight loss (means = -2.6%) than patients with all other carcinomas (means = -9.8%; p = .008). No differences in toxic responses were observed despite larger radiation field size in the tube-fed group (p = .02). Serum albumins in both groups dropped during radiation therapy, with no difference between groups. The tube-fed group maintained higher caloric and protein intakes (35 to 42 kcal/kg, 1.2 to 1.6 gm protein per kilogram) than the oral-fed group (15 to 34 kcal/kg, 0.3 to 1.3 gm protein per kilogram). No differences in body weights were observed between the tube-fed (means = 3.8%) and the oral-fed (means = 3.3%) patients with nasopharyngeal carcinoma. Patients with oropharyngeal and recurrent nasopharyngeal carcinoma had significantly less weight loss with tube feeding (means = 0.2%) than with oral feeding (means = -7.3%; p = .005); thus, tube feeding is recommended during radiation therapy in such patients.
We treated 98 previously untreated patients with stages III and IV resectable epidermoid carcinoma of the oral cavity, oropharynx, and larynx with surgery and postoperative radiation therapy. The reasons for postoperative radiation therapy were unsatisfactory surgical margins in 36 patients, cervical metastases at multiple levels pathologically in 49, and both in 13. Historically, patients with similar findings, treated by surgery alone at our institution, had a relapse rate above the clavicles of more than 70% within two years. In the present series only 15% have had relapses above the clavicles, and distant metastases developed in another 20%. In addition, approximately 6% of patients per year have had second malignant neoplasms develop, predominantly in the esophagus or the lung. These changes in the patterns of failure have implications for future studies aimed at improving the cure rate and the survival of these patients.
Between 1970 and 1980, we treated 107 previously untreated patients with biopsy-proven carcinoma of the nasopharynx by megavoltage external radiation therapy to the primary site, base of the skull, and both sides of the neck. Eighty-seven percent of the patients had stage IV disease (American Joint Committee 1980), 53% had T4 primaries, and 73% had palpable cervical metastases. The histology was anaplastic or poorly differentiated carcinoma in 81%. The observed 5-year survival rate was 35% for the patients treated between 1970 and 1976, and increased to 72% for those treated between 1977 and 1980 (P less than 0.01). The two patient populations were similar except that the dose of irradiation (median and modal) to the primary site was 6,000 rad during 1970-1976 and 7,000 rad during 1977-1980. The survival rate was not significantly influenced by age, sex, birthplace, histology, or stage. These data suggest that a relatively high cure rate might be possible in carcinoma of the nasopharynx, even though most patients present with locally advanced disease. The patterns of relapse are discussed.
Previous studies of nutritional support in cancer patients have applied parenteral techniques for relatively short periods. The purpose of this prospective, randomized trial was to evaluate the efficacy of long-term enteral alimentation in patients at high risk for malnutrition during oncologic treatment. Forty patients with inoperable squamous carcinoma of the nasopharynx and oropharynx were randomized to either optimal oral nutrition or to intensive nasogastric tube feedings during radiation therapy for an average of 8 weeks. Dietetic counselling and oral supplements were provided to both groups. Body weight, dietary intake, and toxicity to therapy were assessed weekly; and serum protein concentrations and anthropometric measurements were made at the time of entry, during the fourth week, at the conclusion of radiation therapy, and 1 month after radiation therapy. Tumor status was assessed at the conclusion of radiation therapy and during routine follow-up, which ranged from 9 to 39 months. The 35 evaluable patients (18 tube fed and 17 orally fed) were comparable with regard to age, disease site, and total radiation dosage, but the tube group had more stage IV patients and a greater median radiation field size. The tube fed group showed no difference in the partial tumor response rate compared with the complete tumor response rate (16 of 18 patients versus 14 of 17 patients), a slightly longer duration of response in those who had recurrence compared with those without recurrence (4.5 months versus 3.4 months) and a similar overall survival pattern to that of the orally fed group. Compared with the orally fed group, the tube fed group had a higher mean caloric intake (39 kcal/kg per day versus 30 kcal/kg per day, p less than 0.001), mean protein intake (1.4 versus 1.1 g/kg per day, p less than 0.01), and in the oropharynx cancer patients, less mean body weight loss (0.6 percent versus 6.1 percent, p less than 0.04) during treatment. The tube fed patients maintained mean mid-arm circumference and recovered mean serum albumin levels after radiation therapy in contrast with the orally fed group. Intensive outpatient tube-feeding nutritional support during radiation therapy in patients with advanced inoperable squamous cancer of the oropharynx significantly improved mean weight maintenance, mean caloric and protein intake, and mean serum albumin levels compared with patients who received optimal oral nutrition. Tumor response to radiation therapy, however, was unchanged.
Between 1949 and 1977, 74 patients with adenoid-cystic carcinoma of various head and neck sites were treated by radiation therapy at Memorial Sloan-Kettering Cancer Center. Radiation therapy alone was employed in 49 patients for recurrent, unresectable disease, and in 25 patients it was given as an adjunct to surgical resection. Among the 49 patients treated with radiation therapy alone, tumor regression was seen in 47 (96%). However, 44 of the 47 (93.5%) subsequently relapsed locally. Relapse occurred within 18 months in one-half of the patients and within 5 years in all of them. Of the 25 patients who received adjunctive radiation therapy about one-half relapsed locally within five years. There were 9 patients in this group, however, whose field size exceeded 8 X 8 cm and the dose of radiation also exceeded 4500 rad: 88% of these patients remained relapse-free at 5 years, compared with only 22% of the other 16 whose dose, or field size, or both, were inadequate by comparison. These data suggest that when irradiation is employed for advanced, inoperable adenoid-cystic carcinoma, it offers useful palliation but is rarely, if ever, curative. Postoperative irradiation, on the other hand, might improve the local control and the survival in patients with operable adenoid-cystic carcinoma who are at high risk for relapse, but only if the field size and the dose are adequate.