Chu H. Chang

The palliation of brain metastases: Final results of the first two studies by the radiation therapy oncology group

Abstract Five schedules of whole brain irradiation ranging from 4000 rad/4 weeks to 2000 rad/ 1 week have been evaluated in two sequential phase III randomized Radiation Therapy Oncology Group (RTOG I studies to determine palliative effectiveness in patients with metastatic brain disease. Improvement in neurologic function status and maintenance of improved or stable neurologic function were utilized as measures of response. All treatment schedules were comparable with respect to frequency of improvement, duration of improvement, time to progression, survival and palliative index. Important prognosticators of response included initial neurologic function and general performance status. Administration of steroids during irradiation favored more rapid improvement; for neurologic-function-3 patients, it increased the overall frequency of improvement. This result must be interpreted with caution since the administration of steroids was not controlled in either study. Patients whose disease is controlled at the primary site and in whom brain is the only site of metastases, constitute a prognostically favorable group; they may benefit from whole brain irradiation to higher doses. This population is currently under investigation in a third RTOG study.

An Operative Staging System and a Megavoltage Radiotherapeutic Technic for Cerebellar Medulloblastomas

CEREBELLAR MEDULLOBLASTOMA is one of the most common types of primary intracranial tumors in children. The treatment of this tumor, unfortunately, is considered as “one of the darkest chapters in pediatric neurosurgery” (1). Cushing (2) reported an average survival of five and six-tenths months in 14 patients with medulloblastoma who received no postoperative radiotherapy. Ingraham and Matson (3) stated that “to our knowledge, no patient with cerebellar medulloblastoma has ever been cured.” Although medulloblastoma has long been known as the most sensitive primary brain tumor to ionizing radiation, the radiotherapy results for this tumor with respect to long-term survival is still very disappointing. In order to better evaluate the response of medulloblastoma to irradiation and to improve the survival rate, the operative records of 100 consecutive cases of tissue-proved medulloblastoma at the Neurological Institute, Columbia-Presbyterian Medical Center were arbitrarily taken in a period from 1940 to 1967 ...

Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas. A joint radiation therapy oncology group and eastern cooperative oncology group study

Recently, the RTOG and ECOG concluded a joint randomized study on malignant gliomas that was in progress for the past five years. A total of 626 patients entered this protocol. Sixty‐seven percent of the 535 evaluable patients have died and thus this represents a preliminary report of a major joint clinical trial. The objective of this study was to evaluate the efficacy after neurosurgery of three new treatment options as compared with control treatment of radiotherapy alone. The four options were: (1) control radiation; 6000 rad/6–7 weeks to whole brain; (2) a higher radiation dose; Control dose plus a booster dose of 1000 rad/1–2 weeks to the tumor; (3) control radiation dose plus BCNU (80 mg/m2/day IV X 3 and repeat BCNU every 8 weeks); (4) Control radiation dose plus combination methyl‐CCNU (125 mg/m2/day orally X 1 and repeat methyl‐CCNU every 8 weeks), and DTIC (150 mg/m2/day IV X 5 and repeat DTIC every 4 weeks). All pertinent patient characteristics were studied and several important prognostic factors have been identified. Notably, age, histologic type (Astrocytoma with anaplastic foci, versus glioblastoma multiforme), initial performance status, time since first symptoms and presence or absence of seizure. At this time, it appeared that there was no treatment option which was significantly better than the control. The study identified that age was the most important prognostic factor. Patients who were younger than age 40 years had an 18‐month survival of 64%, patients who were age 40–60 years had an 18‐month survival of 20%, and patients who were older than age 60 had an 18‐month survival of 8%. The study also demonstrated that a modified histologic classification of anaplastic astrocytoma versus glioblastoma provided better prognostic information than the astrocytoma grading system of Kernohan. Patients with anaplastic astrocytoma had a median survival of 27 months as compared to 8 months for patients with glioblastoma. In further evaluation of any beneficial effect of chemotherapy, it was identified that only among the 40–60‐year‐old groups, BCNU treated patients appeared to have significantly increased survival than patients in the control groups (P = 0.01, one‐sided). Similarly, methyl‐CCNU + DTIC was suggestively better than the control (P = 0.08, one‐sided). The higher radiation dose, 7000 rad/8–9 weeks appeared to give no significantly better survival over the control dose option. Both BCNU and methyl‐CCNU + DTIC produced some toxicity. The combination of methyl‐CCNU + DTIC was more toxic than BCNU, producing severe or worse thrombocytopenia in 23% of the patients as compared to 6% on BCNU.

Midline pineal tumors and suprasellar germinomas: highly curable by irradiation.

Sixty-one patients with midline pineal tumors and 16 patients with suprasellar germinomas were treated with surgical decompression and relatively high-dose radiotherapy of the primary site. Results were excellent, and there were no long-term complications. Ten per cent of midline pineal tumors and 37% of suprasellar germinomas metastasized to the cerebral or spinal subarachnoid space within 6 months to 5 years. Irradiation of the entire neural axis is recommended for locally extensive tumors, simultaneous pineal and hypothalamic lesions, and all biopsy-proved germinomas. The five-year survival rate was 79% for midline pineal tumors and 77% for suprasellar germinomas.

Medulloblastoma in children: A correlation between staging and results of treatment

Abstract Fifty-nine children with cerebellar medulloblastoma were followed prospectively after they were staged and treated consistently with postoperative megavoltage radiotherapy to the entire neural axis. The probabilities of surviving 5 and 10 years were 40.4% and 30.9% respectively; a gradual reduction of the survival rates was observed as the T -category of the tumor increased: i.e. 5 year survival rate was 75% for T 1 , 50.5% for T 2 , 32.3% for T 3 and 0 for T 4 . Children without gross nodular seeding in the subarachnoid space ( M 0 − M 1 ) had better survival rates than children with gross nodular seeding ( M 2 − M 3 ). Improved survival rates were observed by increasing the dose of radiation to the posterior fossa. Among children who had similar surgery, those who had T 1 − T 2 tumors fared better than those with TP 3 − T 4 tumors. The short term (up to 4.5 years) survival rates were better for older children but younger children had better long term survival rates. The posterior fossa was involved in 59% of children who developed recurrent tumor; however, in 75% of the recurrent cases either the posterior fossa was not involved or concomitant involvement of another site also was present.

THE ROLE OF RADIATION THERAPY IN CANCER OF THE EXTRA-HEPATIC BILIARY SYSTEM: AN ANALYSIS OF THIRTEEN PATIENTS AND A REVIEW OF THE LITERATURE OF THE EFFECTIVENESS OF SURGERY, CHEMOTHERAPY AND RADIOTHERAPY?

Abstract An analysis of the role of radiotherapy in the management of gallbladder (GB) and extra-hepatic bile duct (EHBD) cancer its based upon thirteen patients irradiated in our hospital and a review of the literature. These patients were treated as part of curative or palliative management in conjunction with surgery, after surgical failure or recurrence, and as the only palliative modality. Doses ranged from 3800 to 7225 rad. Significant palliation was obtained in 92% of the patients; average total bilirubin value decreased from 9.1 mg.% before to 1.7 mg.% after radiotherapy. The mean survival of all patients was 12.7 months after surgery (7.1 in GB, 16.1 in EHBD), and was 7.3 months after initiation of radiotherapy (6.3 in GB, 8.0 in EHBD). Two patients were alive and well with no evidence of disease 12 and 16 months after radiotherapy, and local tumor control was achieved in two. Complications included possible biliary fibrosis. Based upon a critical review of the surgical, chemotherapeutic, and radiotherapeutic literature, it is concluded that present surgical therapy fails because of extensive regional disease in which local recurrences follow various simple and radical surgical maneuvers; palliative surgery often fails. Survival rates have been poor following any therapy at present, although encouraging results are seen with carefully planned megavoltage radiotherapy. A proposal its made to evaluate the role of radiotherapy systematically: as part of curative therapy post-operatively to decrease local recurrences and to increase the length and quality of survival; to treat incisional recurrences; as part of advanced disease management to increase the effectiveness and length of palliation; and in conjunction with chemotherapy to further consolidate therapeutic gains made with radiotherapy alone.

Quality of long-term survival following irradiation for intracranial tumors in children under the age of two

Abstract Thirty-eight children aged two and under who received radiotherapy alone or post-operatively for primary intracranial tumors from 1957 to 1974 were retrospectively studied for survival rate, late radiation sequelae, and quality of survival. There were 24 deaths, all attributed to the primary disease or its complications. The five, ten, and fifteen year absolute survival rates were 50 %, 39 %, and 38 % respectively, with posterior fossa tumors faring best. The 14 survivors, aged 6 to 21 1 2 years, were evaluated fore physical, neurologic, endocrinologic, and psychologic abnormalities. Eight were found to have minimal or no abnormal neurologic findings, 11 were within the educable range on formal intelligence testing, and 12 had Karnofsky performance scores of 70 or better. There was little clinical evidence of severe endocrinologic dysfunction except for short stature in three. patients correlated with a dose of greater than 3600 rad to the hypothalamic-pituitary region. The patients were assigned to a proposed “Composite Quality of Survival Scale”(CQS) graded 1 to 5 based upon their overall quality of life evaluation. Eight of the patients were rated Grade 3 or better, with three patients essentially normal in most respects. We conclude that the data justify the continued use of radiotherapy in the treatment of very young children with brain tumors. However, there is the obvious need for further optimization of radiotherapy factors (time, dose, volume) in order to minimize the potential late effects of radiation to the central nervous system.

Does extent of surgery influence outcome for astrocytoma with atypical or anaplastic foci (AAF)? A report from three Radiation Therapy Oncology Group (RTOG) trials

Abstract103 patients with the diagnosis of AAF were identified from the RT/BCNU arms of 3 RTOG malignant glioma trials. Pre-treatment tumor size was < 5 cm for 48% and ≥ 5 cm for 52%, and tumor sites were frontal lobe in 55%, temporal in 25%, and parietal in 16%. Surgery consisted of biopsy for 30%, partial resection for 56%, and total resection for 14%. Extent of surgery correlated with age, with 81% of patients < 40 undergoing partial/total resection vs. 60% of those over 40 (P = 0.019).The median survival time (MST) of patients undergoing partial/total resection was 49 mo., vs. 18 mo. for those biopsied only (P = 0.002). Patients with frontal location had longer MST than those with non-frontal lesions (MST: 49 vs. 25 mo., P = 0.047), while no survival difference was apparent by univariate analysis of tumor size. Multivariate analysis demonstrated that only younger age, frontal location, and smaller tumor size correlated significantly with extended survival. Extent of surgery was not predictive.The close correlation between young age and extensive surgery obscures the survival advantage for greater surgery seen with univariate analysis. Smaller tumor size and frontal location favorably influence outcome even when adjusted by age.

Treatment results of craniopharyngiomas

Treatment results on 109 patients with craniopharyngioma treated surgically or by combined surgery and radiation therapy are reported. The five‐ and ten‐year survival rates were 62.9% and 48%, respectively, for 74 patients treated primarily with surgery. For 32 patients treated with combined surgery and radiation therapy, the survival rates were 82.2% and 71%. The 74 patients treated with surgery but no radiotherapy had five‐ and ten‐year relapse‐free survival rates of 31.5% and 17.4%, respectively, and for the 32 patients treated with combined surgery and radiation therapy, these relapse‐free survival rates were 76.3% and 43.8%, respectively. The survival and relapse‐free survival rates were better for children. Morbidity and mortality were higher in patients who were reoperated on for recurrent tumors. Our data indicate that radiation therapy should play a major role in the initial combined management of cranio‐pharyngiomas especially when the lesion cannot be totally resected and when postoperative CT scan shows residual tumors. Cancer 47:847–852, 1981.

Carcinoma of the prostate: treatment with external radiotherapy

In recent years external radiotherapy has been selected as primary treatment of patients with carcinoma of the prostate localized to the pelvis. Among 146 patients treated with external radiotherapy at Columbia‐Presbyterian Medical Center, the 5 and 10 year survival rates were 64.1% and 40.5%, respectively. The 5‐year survival rate was 88.2% for patients with Stage A, 86.8% for Stage B and 58% for Stage C; it was 64.4% for patients with more differentiated carcinomas, but only 28.7% for patients with undifferentiated tumors. Patients with obstructive changes on IVP had a 5 year survival rate of 24.1%, whereas, for patients with no obstruction on IVP, this rate was 71.3%. When radiotherapy started within 6 months after the diagnosis, the 5 year survival rate was 70.3%, whereas, a delay in starting radiotherapy, for more than 6 months after the diagnosis, was associated with a survival rate of 31.9%. Radiation dose of 6500 rad or more was associated with a 5‐year survival rate of 86.7%, whereas, for a dose of less than 6500 rad this survival rate was 57.1%. All the above differences were statistically significant (p < 0.05). Other factors that were examined and were found to influence the prognosis to a degree that was not statistically significant included: age of the patient at the time of radiotherapy, presenting symptoms, levels of acid phosphatase in the serum and in the bone marrow and size of the irradiated volume. In agreement with other published series the complications were usually mild and their incidence low. Tumor involving and protruding into the urethra may have contributed to the formation of urethral strictures. Local control of this cancer with external radiotherapy appears very successful. Treatment failures were manifested most often with distant metastases with or without local recurrence, suggesting that subclinical distant metastases might have been present prior to initiation of radiotherapy. External radiotherapy rather than brachyterhapy, appears to be the treatment of choice for cancer of the prostate with indications for radiotherapy.