Palliative radiotherapy in the management of pancreatic carcinoma: combined interstitial and external beam therapy.
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Adult↗
Biomedical subjects
W C Constable
Publications and source records attributed to W C Constable.
The effect of hyperthermia on radiation-induced carcinogenesis.
Ten groups of mice were exposed to either a single (30 Gy) or multiple (six fractions of 6 Gy) X-ray doses to the leg. Eight of these groups had the irradiated leg made hyperthermic for 45 min immediately following the X irradiation to temperatures of 37 to 43 degrees C. Eight control groups had their legs made hyperthermic with a single exposure or six exposures to heat as the only treatment. In mice exposed to radiation only, the postexposure subcutaneous temperature was 36.0 +/- 1.1 degrees C. Hyperthermia alone was not carcinogenic. At none of the hyperthermic temperatures was the incidence of tumors in the treated leg different from that induced by X rays alone. The incidence of tumors developing in anatomic sites other than the treated leg was decreased in mice where the leg was exposed to hyperthermia compared to mice where the leg was irradiated. A systemic effect of local hyperthermia is suggested to account for this observation. In mice given single X-ray doses and hyperthermia, temperatures of 37, 39, or 41 degrees C did not influence radiation damage as measured by the acute skin reactions. A hyperthermic temperature of 43 degrees C potentiated the acute radiation reaction (thermal enhancement factor 1.1). In the group subjected to hyperthermic temperatures of 37 or 39 degrees C and X rays given in six fractions, the skin reaction was no different from that of the group receiving X rays alone. Hyperthermic temperatures of 41 and 43 degrees C resulted in a thermal enhancement of 1.16 and 1.36 for the acute skin reactions. From Day 50 to Day 600 after treatment, the skin reactions showed regular fluctuations with a 150-day periodicity. Following a fractionated schedule of combined hyperthermia and X rays, late damage to the leg was less than that following X irradiation alone. Mice subjected to X rays and hyperthermic temperatures of 41 and 43 degrees C had a lower median survival time than the mice treated with hyperthermia alone. This effect was not associated with tumor incidence.
Animals↗
The effectiveness of treatment of lymph nodes in cancers of the pyriform sinus and supraglottis.
Three hundred and twelve patients with pyriform sinus or supraglottic cancer were reviewed with respect to effectiveness of therapy upon nodal control. All patients had a minimum 3-year follow-up. Combined modality therapy (radiotherapy and surgery) conferred a higher neck control rate for both N0/N1 and N2/N3 nodes than moderate dose (50 to 60 Gy) radiotherapy alone. Neck dissection appeared to be a significant component of therapy for all neck stages. Fixed nodes, a subset of N2/N3 disease with a very poor prognosis, required combined modality therapy for the best nodal control rates. Downstaging to pN0 with preoperative radiotherapy provided superior nodal control and survival rates.
Carcinoma, Squamous Cell↗
The prognostic significance of lymph node involvement in pyriform sinus and supraglottic cancers.
Three hundred and thirty-three patients with carcinoma of the pyriform sinus or supraglottis were reviewed with regard to lymph node involvement and prognosis. All patients were treated with curative intent and had a minimum follow-up of 3 years. Every patient was restaged according to the AJCC, 1983 recommendations. In addition, nodal fixation to cervical fascia or muscle was evaluated with regard to prognosis. Seventy-five percent (89/119) of the pyriform sinus cancer and 47% (101/214) of the supraglottic cancer patients presented with clinically palpable cervical nodes. The distribution of patients according to N stage was 143 (43%), 84 (25%), 58 (17%), 48 (14%) for N0, N1, N2, N3 respectively. In patients where information on nodal fixation was available, 29% had fixed nodes. No difference in prognosis was noted between N0 and N1 or N2 and N3 stages, and these groups were therefore combined. The 3-year survival was 85% for T1 (N0/N1), 77% for T2 (N0/N1), 63% for T3 (N0/N1), and 65% for T4 (N0/N1) cases compared to 19% for T1 (N2/N3), 34% for T2 (N2/N3), 33% for T3 (N2/N3), and 32% for T4 (N2/N3) cases demonstrating that N stage predominates over T stage with respect to survival. Both the local recurrences and distant metastases increased as N stage advanced. A noteworthy difference between patients with fixed nodes and mobile nodes was found with regard to neck recurrence (35% versus 17%), distant metastases (33% versus 19%) and survival (27% versus 58%). In conclusion, nodal stage is a highly significant determinant of survival independent of T stage in cancers of the pyriform sinus and supraglottis. N0, N1 status and mobility were predictive of a favorable prognosis as opposed to N2, N3 status and fixation. These findings were consistent when the pyriform sinus cancers and supraglottic cancers were analyzed separately.
Humans↗
Primary malignant mediastinal germ-cell tumors and the contribution of radiotherapy: a southeastern multi-institutional study.
A retrospective review was performed by a multi-institutional study group to determine the contribution of radiotherapy to the management of primary malignant mediastinal germ-cell tumors. Twenty-seven patients diagnosed with a primary mediastinal germ-cell tumor between January 1965 and July 1985 form the basis of this study. Twenty-five of the 27 patients were male. Thirteen patients' tumors were diagnosed as seminoma and the remaining 14 patients' tumors had other germ-cell histologies. The single most important prognostic factor was histology, with a 5-year actuarial survival of 100% for the seminomas and only 8.8% for the remaining germ-cell varieties. If total surgical extirpation is not possible, biopsy may be adequate. Of the patients with seminoma, 11 of 12 had local control, and 3 of the 12 patients were treated with doses between 3,000 and 3,100 cGy. High doses for this variety of mediastinal germ-cell tumor might not be required. For the germ-cell tumors other than seminoma, no patient had local control with doses over the range of 3,000-4,750 cGy.
Adolescent↗
Pelvic recurrence of rectal cancer. Options for curative resection.
Pelvic recurrence is an ominous event after curative resection of rectal cancer and is rarely amenable to re-resection by conventional methods. A method to permit a composite resection of these using the abdominal sacral approach has been described previously. This report updates that experience with resection of pelvic recurrence of rectal cancer in 28 patients. Of these, 24 were done with curative intent, and four were done for palliation (mainly for infected or fungating tumor). All patients had extensive preoperative evaluation by clinical and radiologic tests, and most patients had a long free interval period of approximately 18 months, after their primary resection. Although 47 patients had exploratory surgery, only 29 had local disease amenable to resection and four had palliative resections. About half the patients had had an abdominoperineal resection, half had had an anterior resection, and one third had had previous efforts to resect the recurrence. All but one patient had been irradiated with 3000-11,000 cGy. All but two patients (of the 24 curative efforts) required a formal abdominosacral resection (through S1-2 in 12, S2-3 in 9, and S4-5 in 1). Over half the patients also required a bladder resection. There were three operative deaths (12%); one patient had a cardiac death immediately after operation and two were septic deaths at 35 and 60 days. The survivors generally had relief of sacral root pain and good motor function; most of those previously employed could return to work. The actuarial 5-year survival rate is 25% and median survival is 36 months. Long-term survival over 48 months was recorded in five of 21 surgical survivors (23.8%). Survival in a historic comparative group of 30 patients treated for local recurrence only (mainly by radiation) was 15 months median, and at 5 years the survival rate was 3% (p less than 0.001). In conclusion, selected patients with pelvic recurrence of rectal cancer may be retrieved by and returned to functional life with the composite abdominosacral resection.
Abdomen↗
Prognostic value of vocal cord fixation with respect to treatment in cancers of the supraglottis and pyriform sinus.
Vocal cord fixation in supraglottic and pyriform sinus cancers has, in the past, precluded management by radiotherapy alone. Ninety-eight patients were reviewed to determine the prognostic effect of vocal cord fixation. The predictive value of cord mobility status after 50 Gy was evaluated with respect to treatment modality. For patients treated with radiotherapy alone, cord mobility status was predictive of recurrence, yielding 3 year recurrence rates of 33.3% (mobile) versus 80% (fixed) [p = 0.04]. Mobile cords after 50 Gy had similar recurrence rates (33.3% vs. 40.0%, p = 0.60) whether treated by radiotherapy or radiotherapy/surgery. Radiotherapy alone may be used in cases when fixed cords become mobile after 50 Gy without compromising cure rates or laryngeal function. Combined modality provides the best results when cords remain fixed.
Adult↗
The response of a solid tumor to X-irradiation as modified by dose rate, fractionation, and hyperthermia.
The KHT sarcoma in C3H mice was exposed to a total dose of 3000 cGy x-irradiation delivered in three equal fractions at intervals of either 48, 72, or 96 hr. The dose rate was high, 212 cGy/min or low, 19 cGy/min. The effect of hyperthermia, 42.5 degrees C for 30 minutes, was determined by inducing the hyperthermia using either water or ultrasound. For radiation alone at high dose rate, tumor control was maximum at a fraction interval of 96 hr. At low dose rate, local tumor control was not influenced by fractionation interval and was not different from the maximum tumor control achieved at high dose rate. Hyperthermia alone was ineffective for tumor control. When high dose rate irradiation and hyperthermia were combined, thermal enhancement was highest at fractionation intervals of less than 96 hr where the effects or irradiation alone were least. At low dose rate, the thermal enhancement was independent of fractionation interval. Only for irradiation at high dose rate was the ultrasound-induced hyperthermia more effective at potentiating the radiation than water bath-induced hyperthermia. A possible explanation for the interaction of the dose rate effect with fractionation and hyperthermia is proposed.
Animals↗
Radiotherapeutic management of cancer of the supraglottis.
One hundred eighty-five patients with cancer of the supraglottis were treated with curative intent by radiotherapy alone or combined with surgery over a 14-year period. Minimum follow-up was 3 years. Sixty-eight percent had Stage III or IV disease. Moderate-dose radiotherapy, with surgery in reserve, was the policy for the early lesions, and yielded a 3-year locoregional control rate of 76% for T1 N0/N1, T2 N0/N1, and T3 N0/N1 lesions combined. In this group, 84% of patients with locoregional control retained laryngeal function. The major complication rate was 4%. Patients with advanced disease were treated with preoperative radiotherapy and surgery, resulting in an overall 3-year no evidence of disease rate of 72%. Adverse prognostic factors in supraglottic cancer were the extent of the primary lesion and the presence of N2 or N3 nodes. Neither vocal cord fixation nor N1 nodes had a negative influence on survival in T3 and T4 disease.
Adult↗
Uncommon variants of cervical carcinoma treated with radical irradiation. A clinicopathologic study of 66 cases.
Although certain histologic types are uncommon in cervical carcinoma, these tumors as a group comprise almost one in five patients. The present study throws some light on the therapeutic approaches that are appropriate. From 1968 through 1978, 396 patients with carcinoma of the cervix were treated primarily with radiation therapy, at the University of Virginia Medical Center. The treatment policy remained consistent throughout the study interval. Diagnostic pathologic material was reviewed and uniformly classified in 365 cases (92.2%). Over 80% were invasive keratinizing or nonkeratinizing squamous cell carcinoma. There were 66 patients with uncommon histologic types including 24 adenocarcinomas (6.6%), 13 adenosquamous carcinomas (3.6%), 10 small cell carcinomas (2.7%), 6 papillary squamous carcinomas (1.6%), 5 glassy cell carcinomas (1.4%), and 8 miscellaneous types (2.2%). These 66 patients form the basis for this report. Five-year survival rates and causes of failure are presented along with management recommendations.
Adenocarcinoma↗
Preoperative radiation therapy for rectal cancer. An effective therapy in need of a clinical trial.
Sixty patients with locally advanced adenocarcinoma of the rectum have been treated with preoperative high-dose pelvic irradiation in an attempt to improve operability and increase local control. Fifty-six patients showed no evidence of distant metastases at surgery and their records have been analyzed with respect to recurrence patterns, survival, and complications. The results have been compared with those of a similar analysis of 106 patients treated with curative surgery alone. There was a statistically significant improvement in local control between groups, with 16% of patients in the radiotherapy group having a component of local failure compared with 40% in the surgery group. A dose response was observed, with 67% local control at 4000 rad (4000 cGy) and 91% local control at 5000 rad (5000 cGy). Despite the more advanced clinical stage of the irradiated patients, no significant difference in survival was seen between groups, with a five-year survival rate of 52% in the irradiated patients and 48% in patients treated by surgery alone. Preoperative high-dose radiotherapy was well tolerated, with a 5% incidence of major complications in both groups.
Adenocarcinoma↗
Dose response to preoperative irradiation in rectal cancer: implications for local control and complications associated with sphincter sparing surgery and abdominoperineal resection.
Sixty patients with locally advanced adenocarcinoma of the rectum have been treated with preoperative high dose pelvic irradiation at the University of Virginia and Rockingham Memorial Hospital. Fifty-six patients showed no evidence of distant metastases at surgery. A dose response was observed with a 67% incidence of local control with 4000 cGy vs. 91% incidence with 5000 cGy. For the 52 patients who received curative surgery, there has been no local failure alone; 6 of these patients have had local plus distant failure and 16 have had distant failure only. Forty-three percent had anterior resection (AR) and 57% had abdominoperineal resections (APR). The major complication rate was 5% and the minor 14%. No increase in complications or decrease in local control was found between APR and AR. Five-year actuarial survival was 64% for lesions limited to the bowel wall, 59% for node negative lesions with disease extending through the wall, and 23% for node positive patients.
Adenocarcinoma↗
Mitomycin and fluorouracil with concomitant radiotherapy in head and neck cancer.
Forty-two previously untreated patients with predominantly stage IV (35) head and neck squamous cell carcinoma were treated preoperatively with mitomycin and fluorouracil and concomitant radiotherapy with 5,000 to 6,000 rad using a split-course technique. Toxic reactions were acceptable. Five patients developed severe mucositis. The white blood cell count fell to 1,500/cu mm in two patients; the platelet count fell to 100,000/cu mm in three. Other complications occurred in three patients. Eighty-six percent of patients completed advised treatment. Complete response, assessed clinically and with histologic correlation, was 79% at primary sites and 69% at nodal sites. Twenty-seven patients had a complete response (64%). Follow-up currently is between ten and 24 months. Though analysis of disease-free intervals and survival data is premature, the high complete response rates in this study are encouraging.
Carcinoma, Squamous Cell↗
Influence of ultrasound-induced hyperthermia and X-irradiation on the incidence of metastases from a solid tumor.
The KHT sarcoma transplanted into mouse legs was treated by X-irradiation, hyperthermia or a combination of X-irradiation plus hyperthermia. Neither 20 Gy of X-irradiation or hyperthermia for 60 min were effective in controlling the local tumors when used alone. Simultaneous treatments, however, resulted in 22% of the tumors being locally controlled corresponding to a TER of 2.0. Local control was increased when irradiation was given 1 h before or after hyperthermia, TER 2.8 and was maximum, TER 2.9, when the hyperthermia was 0.1 h after irradiation. When the local tumor was controlled by irradiation alone or by irradiation delivered 1 h before or after hyperthermia, all of the metastases that subsequently occurred arose before or during treatment. When tumors were locally controlled by radiation given during or immediately after hyperthermia, metastases developed that must have occurred as a consequence of the treatment. The treatment sequence that resulted in a maximum TER for tumor control did not correlate with the risk of metastatic spread. The timing of the irradiation in relation to hyperthermia may explain some contradictory findings regarding the influence of heat on the incidence of metastases. Hyperthermia did not affect the distribution of anatomic sites involved with metastases or the ratio of lymphatic to hematogenously spread metastases.
Animals↗
Carcinoma of the middle ear and external auditory canal.
Thirty-one patients with malignant tumors of the middle ear and external auditory canal (EAC) were observed at the University of Virginia Hospital from 1956 through 1980. Of 27 patients with carcinoma, 21 had squamous cell carcinoma, 4 had basal cell carcinoma and 2 had adenoid cystic carcinoma. One Ewing's sarcoma and 3 rhabdomyosarcomas occurred in an age group of one to 10 years. The 27 patients with carcinoma are reviewed with regard to clinical presentation, treatment modality, results and complications. The majority (67%) of patients had a history of chronic ear drainage, 22% had a previous mastoidectomy or polypectomy and 7% had an associated cholesteatoma. The treatment modalities employed depended on the extent of disease and the patient's general condition. Eighty percent of patients with carcinoma limited to EAC were alive and well at 5 years, compared to 43% of patients with involvement of the middle ear. Fifty-six percent of patients without invasion of the petrous bone were alive at 5 years compared to only 20% of patients with petrous bone involvement. The data strongly suggest that survival depends on the extent of disease. The corrected disease free 5 year survival rates were 14% for patients who had surgery alone and 50% for those who had surgery and radiotherapy. Of the three patients with advanced disease who received radiotherapy alone, none survived five years. Surgery or radiotherapy alone is not sufficient for most of the cases of carcinoma of the middle ear, since these patients often present with advanced disease. We recommend combined therapy, especially postoperative radiotherapy, except for early lesions that do not involve the mastoid or petrous bone. Other series suggest radiotherapy would be adequate and more effective than surgery for early lesions. Surgery will provide the diagnosis, determine the extent of disease, offer adequate drainage of infected material and relieve most pain before radiation therapy.
Adult↗
Topical use of N-acetylcysteine for reduction of skin reaction to radiation therapy.
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Acetylcysteine↗
Effect of ultrasound-induced hyperthermia and cis-diamminedichloride platinum II on murine renal function.
Murine renal function was evaluated after ultrasound-induced kidney hyperthermia (42.5 degrees C and 46.5 degrees C for 35 minutes) and the administration of cis-diamminedichloride platinum II (8 mg/kg). A quantitative immunonephelometric technique was employed to determine urinary total protein (TP) and albumin (Alb) 1-180 days post-treatment. Hyperthermia of 46.5 degrees C elevated urinary TP excretion significantly more than that of 42.5 degrees C cis-diamminedichloride platinum (Cis DDP) administration greatly increase urine TP with a peak mean TP concentration of 488 microgram/ml, four days after Cis DDP (normal range was 26-48 microgram/ml). This returned to normal by day 14. The TP excretion after 42.5 degrees C hyperthermia with concurrent Cis DDP was similar to Cis DDP alone, implying there was no potentiation of early or late Cis-DDP-induced renal damage by hyperthermia. Late mouse mortality was greater (P = 0.08) after Cis DDP alone, than Cis DDP with 42.5 degrees C hyperthermia. There was a statistically significant increase (P less than 0.05) in the Alb/TP excretion ratio after the addition of 42.5 degrees C hyperthermia to Cis DDP, implying an alteration in the site or nature of the Cis DDP renal lesion by hyperthermia.
Albuminuria↗
CT scanning and interstitial therapy.
Computerized tomography is of considerable value in determining tumor volume at many anatomic sites that are otherwise difficult to visualize. The ability to define volume accurately by means of a CT scan can be employed in interstitial radiotherapy. First, CT scan information may be used to plan the implant volume by defining the tumor location and extent prior to implantation of radioactive materials. Second, radioactive sources and/or afterloading devices can be localized after implantation by means of a CT scan. Third, follow-up of tumors to assess both tumor regression and recurrence is facilitated.
Brachytherapy↗