Breast cancer. Importance of adequate surgical excision prior to radiotherapy in the local control of breast cancer in patients treated conservatively.

The extent of excision performed for mammary carcinoma prior to radiotherapy as a risk factor for local recurrence was studied in 503 patients. Three hundred twenty-three tumors (62%) were excised with a minimal rim of tissue (tumorectomy). One hundred forty-two patients (27%) had wide excision and 56 (11%) had quadrantectomy. Tumor stage, size, and radiation treatment were similar for all groups. Forty-one percent of tumorectomies had involved margins, and only 14% and 7% were involved in the wide excision and quadrantectomy groups, respectively. Local failure was 15% for tumorectomy, 7% for wide excision, and 5% for quadrantectomy. In T1 ductal carcinoma, only 4% of those with excisions greater than 5 cm had recurrences. Lesser excision had 20% recurrence. Extent of excision before radiotherapy is an important risk factor for recurrence. Failure was inversely proportional to the amount of breast tissue resected. Narrow excision should be discouraged since a larger tumor burden remains that may not be sterilized by radiation.

Significance and therapeutic implications of tumor regression following radiotherapy in patients treated for squamous cell carcinoma of the oropharynx and pharyngolarynx.

The prognostic significance of tumor regression following radiotherapy was evaluated in 1,897 patients with oro- and pharyngolaryngeal cancer. Complete tumor regression occurred in 62% and 80% at the end of treatment and 2 months later, respectively. Complete regression was significantly higher for early tumors than for advanced stages and for exophytic lesions compared to deeply infiltrative cancers. Depending on tumor location, 75% to 90% of T1, T2 stages and 50% to 80% of more advanced tumors were locally controlled in patients who experienced complete tumor regression at 2 months. The local failure rate was at least 80% for those who did not have complete regression. The local failure rate for the incomplete responder was the same for early and advanced tumors. Complete tumor clearance following radiotherapy is a reliable indicator of permanent local control. Tumor regression after a dose of 5,000 to 5,500 cGy should be used as a guide to select patients who could be treated by either radical irradiation or surgery.

Desmoid tumors in adults: the role of radiotherapy in their management.

Twenty-six adult patients with the pathologic diagnosis of desmoid tumor were treated between 1964 and 1983 at the Institut Curie in Paris with megavoltage irradiation. Twenty of these patients (76 percent) had extraabdominal tumors. Definitive surgical resection was performed on nine patients (one received preoperative radiotherapy). At last follow-up 1 1/2 to 10 years after treatment, all of the patients had no evidence of disease. Seven of the nine had follow-up examinations from 5 to 10 years after treatment. Seven patients had postoperative radiotherapy with doses from 4,700 to 6,500 rads (47 to 65 Gy) for either microscopic (three patients) or gross (four patients) residual disease. All but one patient had no evidence of disease from 2 to 8 years after treatment. Nine patients had radiotherapy for recurrent inoperable tumors and six had no evidence of disease from 3 to 20 years after treatment. Recurrences developed in three patients; outside the treatment portal in one, and the other two had received less than 5,000 rads (50 Gy). Clinical regression of tumors after treatment was slow, with complete regression taking up to 2 years. Postoperative radiotherapy with doses of at least 5,000 to 6,000 rads (50 to 60 Gy) was effective in achieving local control of inoperable or incompletely resected tumors, thus the need for repeated resections was avoided. Computerized tomography has greatly improved the assessment of tumor extension and should be used routinely before either operation or radiotherapy to obtain adequate margins and minimize the chance of missing disease.

Treatment of metastatic neck nodes secondary to an occult epidermoid carcinoma of the head and neck.

One hundred thirty-eight patients, who were followed for a minimum of 5 years, had either surgery and postoperative radiotherapy (48 patients) or radiotherapy only (90 patients) for metastatic epidermoid carcinoma in cervical nodes from an unknown head and neck primary. All received radiotherapy to the presumed occult sites. Forty-five percent presented with a single unilateral adenopathy. Those who were initially operable had a neck recurrence rate of 17% and a survival rate of 53%. Forty-three percent of initially inoperable patients recurred and only 25% survived. Patients with adenopathy which completely regressed or became resectable after irradiation had an 80% locoregional control. Only 4% developed an overt cancer at an occult site within 5 years.

Is it necessary to irradiate the breast after conservative surgery for localized cancer?

Two hundred one patients with operable breast cancer received postoperative irradiation after limited surgery and were followed up for five years. Fifty-three patients (26%) had positive margins. The breast cancer recurrence rate at five years was 14%, less than half the incidence reported for patients treated by limited surgery only. Those with positive margins who received irradiation had a recurrence rate of only 13%. Another 324 patients with tumors (less than or equal to 3 cm) N0 who were treated similarly were evaluated for distant dissemination in relation to local control. Patients who remained free of local disease or developed recurrences more than five years after treatment had significantly better distant disease-free and overall survival than patients who failed locally within five years. Breast irradiation after conservative surgery resulted in decrease in local recurrence and reduced the need for salvage mastectomy. Long-term follow-up of a large number of patients is necessary to determine the relation between local control and the decreased risk of distant dissemination.

Comparison between the nuclear diameters of primary and metastatic breast cancer cells obtained by cytologic aspiration.

In order to determine if there are morphologically identifiable characteristics between malignant cells obtained from a primary cancer and its metastasis the nuclear diameter was used as an indicator of the degree of malignancy, since there is good correlation between nuclear size, DNA content, and chromosome numbers. The nuclear diameter of primary and metastatic mammary carcinoma cells, obtained by cytologic aspirates, was measured by ocular micrometry. The purpose was to investigate whether a cell population at the primary site developed, at the metastatic sites, a population with the same nuclear size or one having larger and more anaplastic nuclei. One hundred eighty-five patients with infiltrating ductal carcinoma of the common variety were examined. The primary cancer and axillary nodal metastasis were examined in 97 patients before treatment. Thirty had cytologic examination of the breast cancer, as well as of the metastasis, which developed 1 to 14 years after treatment. Eleven were examined before radical breast irradiation and again at the time of relapse in the breast. Forty-seven had bilateral synchronous mammary carcinoma and both primary cancers were studied. The data presented indicate that there is extreme similarity between the nuclear diameters of the primary tumor and its metastasis. This similarity persists for several years regardless of both the location of the recurrence or radical irradiation. These results support the view that the majority of tumors are monoclonal in origin. The clone that invades the metastatic site appears to be the same as the one that initiated the primary cancer. In contrast, the nuclear diameters of cell populations obtained from synchronous bilateral breast cancer were dissimilar, indicating that they arose from separate clones of malignant cells.

Limited surgery and radiotherapy in the treatment of localized breast cancer. An overview.

Conservative surgery and modern radiotherapy has been found to be as effective as mastectomy in treating early breast cancer. There is no difference in survival or local control. Irradiation following tumorectomy has a low incidence of complications, and yields excellent cosmetic results and breast preservation.

Prognostic significance of clinical nodal involvement in patients treated by radical radiotherapy for a locally advanced breast cancer.

A group of 230 female patients, treated between 1960-1976 with radical megavoltage radiotherapy for locally advanced breast cancer (T3 greater than 7 cm-T4 Stage), was analyzed retrospectively. Those with inflammatory cancer or evidence of disseminated metastatic disease were excluded. Clinical axillary nodal involvement appears to be a very important prognostic feature. Actuarial disease-free survival at 5 years for the 109 patients with clinically negative nodes (N0N1a) is 52%; whereas it is 28% (p less than 0.001) for the 121 patients with clinically involved nodes (N1b, N2-N3). The 5-year survival following salvage surgery, which was performed on 92/230 patients (40%), correlated with the initial nodal status. It is 62% for the N0 group, but only 27% for those with clinically involved nodes. The survival of the 138 (60%) patients who were treated by radiotherapy only is similar to that obtained in patients who had secondary salvage surgery. This study reinforces the need to stratify patients with locally advanced breast cancer according to the initial clinical status of the axilla when either therapeutic trials are contemplated or the results of treatment are reported. Adjuvant systemic treatment should be strongly considered in patients with clinically involved nodes, since the survival obtained by local treatment alone is poor.

Radiation treatment of lateral epilaryngeal cancer. Prognostic factors and results.

Treatment results of epilaryngeal cancer are rarely individualized in the world literature. For this purpose, we have reviewed the records of 167 patients with squamous cell carcinoma of the lateral epilarynx who received radical radiotherapy at the Institut Curie on a megavoltage unit, between 1959-1975. Two-thirds of the lesions were located at the junction of the ary- and pharyngo-epiglottic folds and lateral border of the epiglottis. Forty-four percent of patients had advanced primary lesions (T3, T4) and over 50% had palpable neck nodes at the time of presentation. The absolute survival for the entire patient population at 3 and 5 years was 44% and 32%. Local control for T1 and T2 tumors at 3 years was about 80%. Survival at 5 years for the N0 Stage patient was 40%, whereas it was about 20% for those with clinically palpable nodes. Patients with exophytic tumors and lesions which regressed completely within 8 weeks following irradiation had a significantly better 3-year survival and local control than those with nonexophytic tumors and with tumors which had incompletely regressed after irradiation. Radiotherapy remains the treatment of choice for the small tumors (T1, T2) but the association of radical surgery with pre- or postoperative radiotherapy should be considered for advanced disease.

Natural cytotoxicity in patients undergoing radiation therapy.

Natural cytotoxicity against K562 target cells was measured in 51 adults with solid epithelial malignant tumors who were untreated, in 42 patients who were studied within 6 weeks following completion of radiotherapy (4,000-7,000 rads), and in 27 normal subjects. In both the radiated and the nonirradiated groups, mean cytotoxicity for patients with localized cancers was not significantly different from that of the normal controls, whereas mean cytotoxicity for patients with advanced cancers was significantly lower than that for normal controls and patients with localized disease. Twelve percent of nonirradiated patients and 13% of radiated patients with localized tumors, but 46% of nonirradiated patients and 44% of irradiated patients with advanced cancers, failed to exhibit normal NK activity. Mean cytotoxicity for irradiated patients was not significantly different from that of untreated patients. PBL from most patients showed enhanced cytotoxicity after preincubation of PBL with interferon (IFN alpha). Mean cytotoxicities for nonirradiated and irradiated patients after IFN alpha pretreatment of PBL were not significantly different. In both patient groups, IFN alpha-boosted killing was significantly less in patients with advanced disease than in patients with local tumors or normals. These results indicated that radiotherapy has no significant effect on spontaneous or IFN alpha-boosted natural cytotoxicity.

Natural cytotoxicity and interferon production in human cancer: deficient natural killer activity and normal interferon production in patients with advanced disease.

Natural cytotoxicity was measured in 51 adult patients with solid epithelial malignant tumors and in 27 normal subjects. Peripheral blood leukocytes (PBL) from 31% of the patients and 7% of the controls failed to kill target cells (K562) in a short-term chromium-release assay. When patients were classified according to clinical stage, PBL from 12% of patients with localized cancers, but 50% of patients with advanced disease, failed to exhibit cytotoxicity within the normal range. Pretreatment of PBL with interferon alpha (IFN alpha) or with Newcastle Disease Virus (NDV), a potent inducer of IFN alpha, enhanced cytotoxicity from all normal subjects. Of patients whose PBL lacked spontaneous cytotoxicity, half were able to kill normally after pretreatment of PBL with IFN alpha or NDV. Virtually all the patients whose PBL were unable to kill despite pretreatment with IFN alpha or virus had disseminated malignancies. IFN alpha production by PBL exposed to NDV and to K562 cells was normal in all the patients regardless of stage of disease or ability to kill K562 cells. The observed defect in natural cytotoxicity is thus unlikely to be due to a failure of PBL to produce IFN alpha.

Elective postoperative radiotherapy after incomplete resection of colorectal cancer.

It is known that patients with incompletely resected epithelial cancers are at high risk of local recurrence. A prospective study to determine whether elective postoperative radiotherapy can decrease the incidence of local recurrence and thus improve survival of those patients with an incompletely resected tumor was made of 125 irradiated patients with locally advanced colorectal cancer (B2, C1, C2) 78 patients had rectosigmoid tumors and 47 had colonic cancers. Complete resection (R0) was performed in 94 patients (75 per cent). Thirteen (10 per cent) had microscopic (R1) and 18 (14 per cent) had gross residual disease (R2). Local control and survival (average follow-up, 38 months) of patients with microscopic residual cancer (RI) were 84 per cent (11/13) and 77 per cent (10/13) respectively. These results were identical to those obtained in patients without residual disease (R0). Patients with gross residual disease (R2) had a local control of 50 per cent (9/18) and a survival of 39 per cent (7/18). Radiation complication occurred in seven of 125 patients (6 per cent). One patient died, of radiation enteritis. One patient required a nephrostomy. The remaining five patients were treated conservatively. Elective postoperative radiotherapy given to patients who had incomplete resection of a colorectal cancer prevented local recurrence in the majority and may have increased survival.

Experience of the Curie Institute in treatment of cancer of the mobile tongue: I. Treatment policies and result.

Six-hundred-two patients were treated for cancer of the mobile tongue between 1959 and 1972. Sixteen percent had T1, 48% T2, and 36% T3 lesions. Sixty-four percent had no palpable nodes (N0). The primary was treated in the majority of patients by radium implant alone or in association with external radiotherapy. Nodes were treated primarily by surgery. Absolute and determinate survivals at five years are 36% and 48%. Determinate survivals for T1, T2 and T3 tumors are 80%, 56%, and 25%. Fifty-nine percent of those with clinically negative neck nodes survived five years. Recurrence at the primary site alone or associated with neck failure is 14% for T1, 22% for T2 and 29% for T3. Seventy percent of recurrences occurred within one year. Although 13% of patients who had recurrences at the primary site were alive at five years, 33% of those who had salvage surgery were rescued. Two percent of patients required surgery for radiation necrosis. In our opinion, radiotherapy remains the treatment of choice for the management of the primary lesion of cancer of the mobile tongue.

Experience of the Curie Institute in treatment of cancer of the mobile tongue: II. Management of the neck nodes.

Treatment of neck nodes of 602 patients with cancer of the mobile tongue was mainly surgical. Three-hundred-eighty-three (64%) were clinically N0, and 244 had elective neck dissection. Thirty-four percent (84/244) had occult metastasis. Thirteen percent (33/244) had major nodal involvement (greater than 3N + and/or extracapsular spread) and received postoperative radiotherapy. Twenty-one percent (7/33) recurred in the neck. Thirty-six percent (12/33) were alive, NED, at five years. Sixty-six percent (160/244) were N-, and 21% (51/244) had minimal nodal disease (less than or equal to 3N+) and did not receive postoperative radiotherapy; recurrence in neck was similar (7% and 14%) as well as the five-year survival (54% and 51%). Twenty-one patients had preoperative radiotherapy to the neck. Only one (5%) experienced recurrence of disease. Fifty had radiotherapy only. Seven (14%) failed in the neck. There were 219 patients who had clinically positive nodes and 120 who had radical neck dissection. One-hundred-one of these patients did not receive preoperative radiotherapy. Sixty-three percent (64/101) had nodal metastasis, and 27% (27/101) had major nodal involvement. In this group of patients, for the same degree of nodal involvement, postoperative recurrences in neck and the survival were similar to that of patients with clinically N0 neck, except for those with major nodal involvement. This latter group had a dismal five-year survival (12%). Nineteen had preoperative radiotherapy, and three (16%) had recurrence of disease in the neck. At present, patients with clinically N0 neck and small primary (less than or equal to 3 cm), who are therefore at low risk of failure at primary, receive brachytherapy and conservative neck dissection. Postoperative radiotherapy is given if major nodal metastasis exists. Those with larger primary (high risk of failure) receive neck irradiation only, since many will require combined resection at a later date. All patients with clinically positive nodes are treated preoperatively with 5500 rads before neck dissection.

The treatment of locally advanced carcinoma of the colon and rectum by a surgical procedure and radiotherapy postoperatively.

Following resection of locally advanced carcinomas of the rectum and colon, 95 patients received moderate dose elective radiotherapy either to an inverted T field or the entire abdomen. In 27 instances, carcinomas invaded adjacent structures and were incompletely resected. Fifty-seven patients had tumors of the rectosigmoid and had either an abdominoperineal or an anterior resection. Thirty-five patients had a mean follow-up period of 26 months. Three of 35 carcinomas recurred locally, 26 of 35 patients are alive without disease. Thirty-eight patients had carcinomas of the colon and had either a partial or hemicolectomy. Thirty-one had a mean follow-up period of 24 months. Five of 31 carcinomas recurred locally. Seventeen of 31 patients are alive, without disease. Sixty-six of 95 patients have survived two years free of disease. One death occurred from radiation enteritis. Radiotherapy postoperatively for patients at a high risk of failure resulted in a low incidence of local recurrence.