Allan O. Langlands

RADICAL RADIOTHERAPY FOR EARLY NONSMALL CELL LUNG CANCER

PURPOSE To evaluate the results of a departmental treatment policy in a consecutive series of patients with nonsmall cell carcinoma of the lung. A second purpose was to estimate the survival of patients treated with radical intent. A third purpose was to estimate the impact of comorbidity on the selection of patients for treatment and on its outcome. METHODS AND MATERIALS The records of 720 consecutive patients referred to a single Department of Radiation Oncology between 1979 and 1985 were reviewed. One hundred fifty patients with early stage (Stage I and II disease) were studied in detail and the results are presented for the outcome of 103 patients treated by radical radiotherapy. All patients were followed for a minimum period of five years or until death. RESULTS Patients referred for radiation therapy were elderly and usually had squamous cell carcinoma of the lung. Comorbidity was significant as was weight loss which occurred in a third of patients. The overall survival of patients treated with radical intent was 13%. In a small subgroup of patients with T1 tumors without weight loss and aged under 70 survival reached 50% at 5 years with no treatment-related mortality and with insignificant treatment-related morbidity. CONCLUSION Highly selected subsets of patients suitable for treatment with radiotherapy can be defined equally as well as highly selected subsets of patients can be selected for surgery. Treatment outcome can be surprisingly good in these subsets indicating that the treatment of nonsmall cell lung cancer, particularly in older patients without comorbidity should not automatically be by a surgical approach.

SYNCHRONOUS 5-FLUOROURACIL, MITOMYCIN-C AND RADIATION THERAPY IN THE TREATMENT OF LOCALLY ADVANCED CARCINOMA OF THE CERVIX

Locally advanced carcinoma of the cervix has a poor prognosis with a high incidence of persistent or recurrent local disease contributing to distressing symptoms and poor survival. This has remained unaltered over the past 30 years in spite of the addition of other therapeutic modalities. Between 1983 and January 1986, 38 patients with locally advanced carcinoma of the cervix were treated with synchronous 5-fluorouracil, mitomycin-C, and radiotherapy. The results of this pilot study indicate both an improvement in pelvic control and in 3-year survival rate for the chemosensitized therapy compared to conventional radiotherapy alone (55% v 28%) using historical controls. Improved survival was only significant for bulky FIGO Stage IIb tumors. The toxicity of this combination was predominantly gastro-intestinal and led to modification of both radiation dose and technique with subsequent improvement in the incidence of side effects. The results suggest that the combination of synchronous chemotherapy with radiotherapy is an improved method of treatment for locally advanced carcinoma of the cervix and that a prospective randomized trial is now justified.

Sarcomas followig radiation therapy for breast cancer: A report of three cases and a review of the literature

Purpose: First to describe clinical and pathologic features of sarcomas arising after radiation therapy for breast cancer and to report three cases of sarcoma arising 7, 15, and 20 years following radiation therapy for breast cancer. Second, to review the literature on this treatment complication. Methods and Materials: Medline literature search. Results: The most frequent histology is osteosarcoma and bone is affected more commonly than soft tissue at a median latency of 11 years. The scapula is the most frequently affected bone. The most frequently affected soft tissue site is now the conserved breast with a median latency of 5.5 years. The aetiologic factors relating to these sarcomas are not fully defined with factors of beam energy, radiation dose, chemotherapy and regional edema being inconsistently reported. Conclusion: The frequency of radiation-induced sarcoma at 10 years of follow-up is approximately 0.2%. This is an overestimate by an unknown factor because of the description of sarcomas arising metachromously in breast cancer patients, in nonirradiated areas

Concurrent 5-fluorouracil, mitomycin C and irradiation in locally advanced cervix cancer.

We reviewed 177 patients treated with radical radiotherapy for locally advanced (FIGO stages IIB, IIIA, IIIB) cervix cancer between January 1979 and December 1989. The radiotherapy was given by external beam treatment to the pelvis and by an intracavitary caesium insertion. Ninety-three patients also received chemotherapy which consisted of infusional 5-fluorouracil during the first and last weeks of the external beam component of the radiotherapy, combined with bolus mitomycin C (group A, 64 patients) or without mitomycin C (group B, 29 patients). These groups were compared with patients treated by radiotherapy alone (group C, 84 patients). The median follow-up was 7.2 years. The median survival time for all patients was 47 months, but was significantly higher (87 months, p = 0.004) for group A. Rates of relapse-free survival and local control were also higher in group A. Toxicity was assessed in detail using the Franco-Italian glossary. There was a relatively high rate of complications, particularly in group A, with 36% of patients having grade 3 or 4 complications. This increase in toxicity persisted through all follow-up time intervals. Patients in group B also demonstrated a higher rate of toxicity than group C, but this increase was limited to the first 6 months of follow-up. The use of mitomycin C in addition to radiotherapy and 5-fluorouracil should be regarded with caution, as other studies have also shown that toxicity is increased, but without improvements in survival.

Breast conservation: long-term australian data

Long-term data on the management of early breast cancer in Australia by conservative surgery and radiation therapy is limited. To examine this issue we reviewed our experience of 131 patients with Stage I or II breast cancer treated between November 1979 and December 1985. Ninety patients had a T1 tumor and 41 a T2 tumor. The extent of surgery varied from a local excision (LE), a wide local excision, to a quadrantectomy or partial mastectomy. Sixty-two per cent of patients also had an axillary dissection. One hundred and nineteen patients were treated using 6Mev photons to the whole breast (Median dose; 50 Gy) +/- regional nodes followed by a single plane Iridium-192 boost to the primary tumor site (median dose; 30 Gy). Ten patients did not receive a boost and two elderly patients were treated with an implant only. The median follow-up of surviving patients was 83 months (range, 51-133 months). Six other patients were lost to follow-up at a median of 48 months (range, 4-62). The pattern of first relapse is: breast alone, 7.0%; breast + distant, 0.75%; breast + nodes, 0.75%; regional nodes only, 0.75%; and distant disease, 18%. The extent of surgery did not influence the probability of a recurrence in the primary tumor region. The time to a breast recurrence ranged from 12 to 127 months (median, 61 months). The 5-year actuarial rate of a breast recurrence was 4.5%. The 5-year freedom from distant relapse was 80%. The complications of treatment were acceptable. These included rib fracture (5%), symptomatic pneumonitis (4%), fat necrosis or fibrosis requiring surgery (4.5%), severe arm edema (4.5%). The treatment of the axilla by both surgery plus radiation therapy was associated with a moderate or severe arm edema rate of 29% compared to 8% for surgery alone and 6% for radiation therapy alone. Our long-term data indicate that conservative surgery plus radiation therapy is associated with low rates of breast cancer recurrence which are independent of the extent of surgical resection. Complications were acceptably low provided that the axilla was treated by surgery or radiation therapy but not by both modalities.

Combined chemotherapy and radiotherapy for patients with breast cancer and extensive nodal involvement.

PURPOSE This retrospective review examines local control, freedom from distant failure, and survival for patients with nonmetastatic breast cancer with extensive nodal disease (> 10 nodes, 45 patients; or > or = 70% involved nodes, if < 10 nodes found, 19 patients). All patients received chemotherapy and radiotherapy following mastectomy. PATIENTS AND METHODS Sixty-four patients were treated between January 1980 and December 1988 at Westmead Hospital, Westmead, NSW Australia. The median follow-up duration for surviving patients was 91.5 months (range, 56 to 121). The median age was 51 years, and the median number of positive nodes was 11. Four successive protocols evolved, each with three phases, as follows: induction chemotherapy (doxorubicin or mitoxantrone, plus cyclophosphamide; three cycles), radiotherapy (50 Gy in 25 fractions to chest wall and regional nodes), then chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF]) of progressively shorter duration. Radiotherapy and chemotherapy were concurrent in the fourth regimen. RESULTS One patient (1.5%) developed local recurrence before distant relapse, and seven patients (11%) developed local and/or regional recurrence simultaneously or after distant relapse. The 5-year actuarial freedom from distant relapse and overall survival rates were 45% and 65%, respectively. Overall survival did not vary significantly by menopausal status, nodal subgroup, or dose-intensity. There were no treatment-related deaths. CONCLUSION Combined chemotherapy and radiotherapy in standard dosage is an acceptable approach following mastectomy for patients with extensive nodal involvement at high risk for local recurrence and distant relapse. This approach should be considered standard best therapy for any randomized trials that examine high-dose chemotherapy or bone marrow transplantation for this subgroup of patients.

Locally advanced breast cancer: Defining an optimum treatment regimen

PURPOSE This retrospective review examines response, local control and freedom from distant failure for patients with locally advanced breast cancer treated by chemotherapy and radiotherapy without routine surgery. METHODS AND MATERIALS 67 patients were treated between January 1980 and December 1988 at Westmead Hospital, NSW, Australia. Median follow-up for surviving patients was 56 months. Four successive protocols evolved, each with three phases induction chemotherapy (adriamycin or novantrone, cyclophosphamide) (three cycles), radiotherapy then chemotherapy (cyclophosphamide, methotrexate, 5-fluorouracil) of progressively shorter duration. Radiotherapy and chemotherapy were concurrent in the fourth regimen. RESULTS Clinical complete response (disappearance of all known disease) after chemotherapy, radiotherapy and additional chemotherapy was 18%, 55% and 79% respectively. Seven additional patients subsequently underwent mastectomy (N = 2), local excision (N = 1) or a radiation boost (N = 4) for a total complete response rate of 90%. Twenty one patients (31%) failed to achieve a complete response (N = 7) or recurred locally (N = 14). The crude 2-year rate of local recurrence was 50% for tumors > 10 cm (N = 10) and 14% for smaller tumors (n = 57) and was not influenced by protocol. Two-year actuarial freedom from distant failure was 67% at 2 years. CONCLUSION Local control can be achieved for patients with locally advanced breast cancer with a primary tumor < 10 cm using chemotherapy and radiotherapy without routine mastectomy.

Undergraduate education about cancer: a survey in Australian medical schools

The goals of undergraduate medical education are to provide a core of basic knowledge, and a framework to permit further development of that knowledge. The structure of teaching and experience in cancer medicine should reflect the increasing importance of cancer in the community. Undergraduate teaching of oncology and its scientific bases is currently fragmented, and in some cases may be deficient. Until now, there have few analyses of what is being taught about cancer at different medical schools. We have undertaken a survey of final year medical students or recently qualified doctors in Australia enquiring about their cancer education. The results indicated that substantial differences existed between the medical schools, and we therefore surveyed the teaching faculty in the schools to determine their view of the validity of the questions we used. Together these surveys showed that significant disparities existed between what the faculty felt should be taught and what students had actually experienced.

Multiple primary tumours in patients treated with radiotherapy for breast cancer

Between January 1954 and March 1964, 3926 patients with primary breast cancer were referred to The Department of Clinical Oncology, Edinburgh. One hundred and eighty patients developed 195 malignancies subsequent to the treatment of their initial breast cancer. Overall, the total number of second tumours was not significantly in excess of the expected incidence in the general population. However, statistical analysis revealed a significant increase in the incidence of rectal, skin and bone tumours. The excess of bone tumours was likely due to radiation exposure. There was not an overall excess of tumours within the irradiated or scattered radiation volume.

The efficacy of combined chemotherapy and radiotherapy in advanced non-metastatic breast cancer

Thirty-five patients with locally advanced (inoperable) breast cancer have been treated based on a regimen of chemotherapy-radiotherapy-chemotherapy. At the completion of all treatment a complete remission rate of 86% was achieved with acceptable toxicity. At a median follow-up of 24 months (range 4-60), relapse at the site of bulk disease occurred in 17% (10% isolated loco-regional relapse) and relapse at distant sites in 34%. The median relapse-free survival was 36 months and the median survival has not yet been reached. Following initial promising results in terms of loco-regional disease control in this group of high-risk patients, the protocol was extended to include 34 patients defined as having locally extensive disease. All patients in this subgroup had undergone a modified radical mastectomy and were categorized as (a) patients in whom the pre-operative clinical findings merited (in our opinion) inclusion in the category of locally advanced (inoperable) disease, (b) patients in whom the primary was operable but in whom extensive involvement of axillary nodes was found (greater than 10 nodes positive or greater than or equal to 70% nodes positive if less than 10 nodes found) and (c) patients without the above characteristics with a primary tumor greater than 8 cm. At a median follow-up of 23 months (range 4-48), loco-regional recurrence occurred in one patient (3%) but distant relapse occurred in 21%. Relapse-free and overall survival was not significantly different to that found in patients with locally advanced disease who did not undergo mastectomy.