James A. Lipsett

Fraction size in external beam radiation therapy in the treatment of melanoma

RTOG 83-05 was a prospective randomized trial evaluating the effectiveness of high dose per fraction irradiation in the treatment of melanoma. Retrospective analysis suggested a dose response curve of melanoma to external beam irradiation as the dose per fraction is increased. RTOG 83-05 randomized patients with measureable lesions to 4 x 8.0 Gy in 21 days once weekly to 20 x 2.5 Gy in 26-28 days, 5 days a week. One hundred thirty-seven patients were randomized and 126 patients were evaluable: 62 patients in the 4 x 8.0 Gy arm and 64 patients in 200 x 2.5 Gy arm. Patient characteristics were essentially identical. Stratification was performed on lesions less than 5 cm or greater than or equal to 5 cm. The study was closed on May 31, 1988 when interim statistical analysis suggested that further accrual would not reveal a difference between arms. Response rate overall was complete remission 23.8%, partial remission 34.9%. The 4 x 8.0 Gy arm exhibited a complete remission of 24.2% and partial remission of 35.5%. The 20 x 2.5 Gy arm exhibited a complete remission of 23.4% and partial remission of 34.4%. There was no difference between arms.

Arm lymphedema in patients treated conservatively for breast cancer: Relationship to patient age and axillary node dissection technique

Arm lymphedema (ALE) was evaluated in 74 patients treated conservatively for breast cancer. ALE was defined based upon measurements performed upon 35 volunteer subjects who did not have and were never treated for breast cancer. Multiple variable statistical analysis of 74 breast cancer patients revealed that age at diagnosis was the most important factor related to the subsequent development of ALE. ALE appeared in 7 of 28 patients (25%) 60 years of age or older but in only 3 of 46 (7%) younger patients (p less than 0.02). Axillary node dissection (AND) was the only other statistically significant factor. For the younger patients, obesity and post-operative wound complications appeared to be contributing factors. For the older patients, AND technique was the only significant factor. ALE developed in only 1 of 10 (10%) of the older patients who underwent AND without splitting the pectoralis minor muscle (PMM), but in 6 of 11 (55%) who underwent AND with PMM split (p less than 0.03). Splitting the PMM during AND did not yield more lymph nodes for pathological analysis nor did it yield a higher incidence of patients with nodal metastases. Neither the use of lymph node radiation therapy fields, radiation to the full axilla, nor systemic chemotherapy was associated with ALE. We conclude that older patients are at higher risk of ALE and that this complication can possibly be reduced by not splitting the PMM during axillary node dissection.

Breast retraction assessment: an objective evaluation of cosmetic results of patients treated conservatively for breast cancer☆

Breast Retraction Assessment (BRA) is an objective evaluation of the amount of cosmetic retraction of the treated breast in comparison to the untreated breast in patients who receive conservative treatment for breast cancer. A clear acrylic sheet supported vertically and marked as a grid at 1 cm intervals is employed to perform the measurements. Average BRA value (+/- standard deviation) in 29 control patients without breast cancer was 1.2 cm (+/- 0.7 cm). Average BRA value in 27 patients treated conservatively for clinical Stage I or II unilateral breast cancer was 3.7 cm (+/- 2.1 cm). BRA values in breast cancer patients ranged from 0.0 to 8.5 cm. Statistical analysis revealed that tumor size, employment of adjuvant chemotherapy and use of separate radiation lymph node fields were not factors in breast retraction. Patients who received a local radiation boost to the primary tumor bed site had statistically significantly less retraction than those who did not receive a boost. Patients who had an extensive primary tumor resection had statistically significantly more retraction than those who underwent a more limited resection. In comparison to qualitative forms of cosmetic analysis, BRA is an objective test that can quantitatively evaluate factors which may be related to cosmetic retraction in patients treated conservatively for breast cancer.

Interstitial implant with interstitial hyperthermia

A Phase I Pilot Study combining interstitial or intracavitary irradiation using 192Ir or 137Cs and interstitial hyperthermia in advanced or recurrent tumors is underway at the City of Hope National Medical Center. Hyperthermia is performed using 0.5 megahertz RF (500 kilohertz) radiofrequency localized current fields. In the implanted volume, a temperature of 41° to 45°C is maintained for 30 to 40 minutes. Hyperthermia is performed prior to irradiation in all patients. All patients had either failed previous conventional treatments, including surgery, chemotherapy and/or radiation therapy, or had advanced malignant tumors which were not felt to be controllable by conventional means. Sixteen lesions were implanted in 15 patients. Of the 16 lesions, 11/16 (68%) achieved complete response, and three had no response or recurred locally. The six patients (100%) receiving interstitial implant and hyperthermia as the primary therapy achieved complete response. Normal tissue complications were minimal. Range of response was three to 13 months. Interstitial thermoradiotherapy appears to be a safe and promising mode of therapy in advanced or recurrent accessible malignant tumors.

Health quality of life and colorectal cancer

Background. Quality of life associated with cancer and radiation treatment includes the dimensions of psychologic and physical well‐being, nutrition concerns/ side effects, and radiation treatment‐related anxiety/adjustment. An understanding of the impact of colorectal cancer and radiation treatment on these aspects of health quality of life can be reached by comparing this diagnostic group to others undergoing similar treatment.

Interstitial hyperthermia and interstitial iridium 192 implantation: A technique and preliminary results

Abstract A simple technique using interstitial hypertbermia in combination with interstitial Iridium 192 implantation is described in detail. This technique was initially tested on swine and later successfully tested on seven patients. The preliminary results of the City of Hope Interstitial Hyperthermia Pilot protocol are stated. The authors feel that this simple technique could be used by any radiation oncologist while performing interstitial implants in selected sites.

Factors affecting cosmetic outcome in breast-conserving cancer treatment : objective quantitative assessment

SummaryA battery of objective measurements of cosmetic outcome was performed on 114 patients who had been treated by breast-preservation techniques for breast cancer. Cosmetic breast retraction, as determined by Breast Retraction Assessment (BRA) measurements, was significantly greater in patients who underwent extensive primary tumor resection, were more than 60 years old, weighed more than 150 lbs, or had a primary tumor in an upper breast quadrant. While use of a local RT boost, per se, was not a significant factor, those patients with high dose and/or large volume local boosts more frequently had marked retraction. Breast telangiectasia and depigmentation (T/D) was related to use of a local RT boost, patient age greater than 60 years, and use of separate nodal RT fields. Breast T/D was significantly more frequent with use of electron beam local RT boost which delivered a boost skin dose exceeding 1600 cGy.Objective quantitative assessments, such as BRA and T/D area measurements, provide data to determine factors related to each type of cosmetic change and thus provide guidelines for optimizing cosmetic outcome. Limiting the extent of primary tumor resection may minimize the amount of breast retraction. Omitting the local RT boost, particularly large volume, high dose boosts, may reduce the frequency of marked cosmetic retraction and skin T/D.

Patient self-evaluation of cosmetic outcome of breast-preserving cancer treatment

Thirty-two patients with Stage I or II breast cancer who had completed conservative breast-preserving treatment were asked to rate their cosmetic outcomes. Within this group, extent of the surgical excision of the breast tumor varied, with biopsy scars ranging from 2 to 19.5 cm. All patients had received external beam radiotherapy, with local boost doses in 17 cases. The average interval between self-evaluation and the completion of radiotherapy was 19 months. Patients completed a questionnaire rating the appearance of the treated breast, the degree of difference between breasts and overall satisfaction with cosmesis. They were asked to describe differences between breasts and to make any additional comments. Appearance of the treated breast was rated good to excellent by 94%, although 88% noted a difference of slight to moderate degree between treated and untreated breasts. Overall, 78% of patients were very to extremely satisfied, while moderate satisfaction was reported by 19%. Reports of breast differences included reduced size of the treated breast (44%), increased firmness (31%), elevation (25%), and skin color changes (22%). Reasons for dissatisfaction included chronic breast pain in 3 patients, breast edema in one and arm edema in one. Two patients wanted the untreated breast reduced in size. Statistically significant inverse relationships were found between the length of the biopsy scar and patient ratings of both appearance of the treated breast and overall satisfaction. These results indicated that although most patients were satisfied with cosmetic results of breast-preserving treatments, they are quite discriminating in their evaluations of differences between breasts. Functional factors such as pain and edema had a negative impact on satisfaction with cosmesis.

Total skin electron irradiation for mycosis fungoides: relationship between acute toxicities and measured dose at different anatomic sites

From June 1978 to June 1986, 50 patients with primary and recurrent mycosis fungoides were treated with total skin electron irradiation (TSEI), using the Stanford technique, to a total dose of 3600 cGy. TSEI was used alone, or in combination with low dose total body photon irradiation, or MOPP. Thermoluminescent dosimeter (TLD) measurements of the prescribed skin dose were obtained on twenty patients. The dorsum of the foot was 24% higher. The axillae, the bottom, and the arch of the foot were significantly underdosed. Frequencies of acute toxicities noted at 2000 cGy were: Skin, Grade I-II (RTOG) 80%. Partial epilation: scalp, 100%; eyebrows and at eyelashes, 20%. Nail dystrophy, 48%. Edema: hands and feet, 44%. Bullae: dorsum of feet, 8%; hands, 4%; and 3600 cGy: Skin, grade III 22%. Total epilation: scalp, 66%; eyebrows and eyelashes, 56%. Nail loss, 38%. Edema: hands and feet, 76%. Bullae: dorsum of feet, 34%; hands, 12%. Conjunctivitis, 4%. Large bullae, were more significant on the dorsum of the feet. Severe moist desquamation occurred in eight patients who had ulcerated lesions on initial presentation. Three patients were hospitalized due to ulceration and skin infection. All patients completed treatment after a short to moderate break. No patient developed skin necrosis, or corneal ulceration. No correlation exists between dose level, degree and onset of toxicity with previous chemotherapy or TBI. We conclude that the overall toxicity of TSEI is well tolerated.

Radical radiotherapy as salvage treatment for relapse of Hodgkin's disease initially treated by chemotherapy alone: prognostic significance of the disease-free interval.

PURPOSE A study was performed to determine the effectiveness of radical radiation therapy (RT) in the treatment of patients with Hodgkins disease who relapsed following initial treatment with chemotherapy alone. METHODS AND MATERIALS A retrospective review of patients treated at City of Hope National Medical Center between 1970 and 1987 revealed a total of 10 patients who received radical RT with curative intent as salvage therapy. RESULTS Complete remission was achieved in eight of the ten patients. Patients had an overall 5-year actual survival of 60% and 10-year actuarial survival of 38%. Relapse-free survival was 30% at 5 years and at 10 years. For the five patients with a disease-free interval (DFI) of at least 12 months prior to radical RT, overall actual survival at 5 years was 100% and relapse-free survival was 60%. Three of the ten patients, all with a DFI > 12 months and in first relapse when undergoing radical RT, were long-term relapse-free survivors. CONCLUSION Radical RT is an effective salvage regimen for select patients with advanced stage Hodgkins disease who relapse following initial treatment with chemotherapy alone provided that relapse is limited to sites which can be encompassed by radical RT fields and the DFI is greater than 12 months. Review of other published series supports DFI > 12 months as a favorable prognostic factor. Comparison to other salvage regimens such as autologous bone marrow transplantation is limited. Reviews of other treatment modalities should perform subset analysis on patients with similar presentations to compare the relative effectiveness of various salvage approaches.