Nancy Kucik

Carcinoma of the nasopharynx: factors affecting prognosis

This is a retrospective analysis of 143 patients with histologically confirmed epidermoid carcinoma of the nasopharynx treated with definitive irradiation. Patients were treated with a combination of Cobalt-60, 4 to 6 MV X rays, and 18 to 25 MV X rays to the primary tumor and the upper necks, excluding the spinal cord at 4000 to 4500 cGy to total doses of 6000 to 7000 cGy. At 10 years the actuarial primary tumor failure rate was 15% in T1, 25% in T2, 33% in T3, and 60% in T4 lesions. The corresponding failure rate in the neck was 18% for N0, 14% for N1, and 33% for N2 and N3 lymphadenopathy. The incidence of distant metastasis was related to the stage of the cervical lymphadenopathy: 16% in patients with N0-N1 nodes compared with 40% in the N2-3 node group. The actuarial 10-year disease-free survival rate was 55% to 60% for T1-3N0-1 tumors, 45% for T1-3N2-3 tumors, 35% for T4N0-1, and 20% for T4N2-3 lesions. The overall 10-year survival rate was about 40% for patients with T1-2N0-1 tumors, 30% for those with T3 any N stage tumors, and only 10% for the patients with T4 lesions. Multivariate analysis showed that tumor stage and histological type, cranial nerve involvement, patient age, and doses of irradiation to the nasopharynx were significant prognostic factors for local/regional tumor control. Increasing doses of irradiation resulted in nasopharynx tumor control in 80% of the patients receiving 6600 to 7000 cGy and 100% of those receiving over 7000 cGy in the T1, T2, and T3 tumors. However, the tumor control rate did not rise above 55% even for doses over 7000 cGy in the T4 lesions. Local tumor control was higher in patients who had simulation (55/78 = 71%) compared with those on whom simulation was not performed (34/61 = 56%) (p = 0.10). Moreover, patients with more than 75% of the reviewed films judged as adequate had 69% primary tumor control (66/96) compared with 53% (23/43) for those with fewer than 75% adequate portal films (p = 0.07).

The incidence of breast cancer following mantle field radiation therapy as a function of dose and technique

BACKGROUND There is an increased incidence of breast cancer following mantle field radiation therapy for Hodgkins disease (HD). We reviewed the experience at the Mallinckrodt Institute of Radiology (MIR) for radiation factors related to the development of breast cancer after mantle field radiation therapy for HD. METHODS The radiation therapy records of 152 women treated with mantle field irradiation for HD at MIR between 1966-1985 were reviewed for the development of breast cancer and treatment-related factors. All patients had a minimum of 5 years of follow-up. The treatment era (1966-1974 vs. 1975-1985), stage of HD, mediastinal dose, axillary dose, maximum dose from the anterior field (anterior d(max) dose), the anterior-posterior:posterior-anterior (AP:PA) ratio, age at the time of treatment, length of follow-up, and history of splenectomy were analyzed as possible contributing factors for the development of breast cancer. The observed number of breast cancers was compared to the expected number based on age-adjusted incidences from the Connecticut Tumor Registry. RESULTS Ten breast cancers occurred in the population. Eight involved an upper outer quadrant. In a multivariate analysis, the development of breast cancer was significantly associated with axillary dose. Patients in the early treatment era were at an increased risk for the development of breast cancer due to high anterior d(max) and breast doses from weighting the fields anteriorly on a low energy linear accelerator. The use of current radiation therapy techniques was not related to an increased risk of breast cancer with a median follow-up of 13 years. CONCLUSIONS A high dose to the axilla and the anterior d(max) point is significantly associated with the development of breast cancer after mantle field irradiation for HD. Efforts to protect the breast from high doses will likely lessen the increased risk of breast cancer in women treated with radiation therapy for HD.

Postoperative radiotherapy for malignant fibrous histiocytoma

Between 1974 and 1989, 49 patients with histologically confirmed malignant fibrous histiocytoma received postoperative radiotherapy at the Mallinckrodt Institute of Radiology for primary (41) or recurrent (8) disease. Median age of the patients was 63 years, and the median follow-up period was 41 months. Patients were grouped according to the 1988 AJC staging classification: stage IA (one patient), stage IIA (4 patients), stage IIB (9 patients), stage IIIA (15 patients), stage IIIB (18 patients), and stage IVA (2 patients). Eight tumors (16%) were in the pelvis, 8 (16%) in the trunk, 4 (8%) in the head and neck, and 29 (60%) in the extremities. Primary surgical procedures included incisional biopsy (4 patients), excisional biopsy (19), narrow margin excision (14), wide local excision (9), and removal of the entire compartment (3). Based on pathology reports, the margins of resection were classified as positive in 23 (5 gross, 18 microscopic), 5 close, 11 negative, and 10 unknown. Patients were irradiated with shrinking field technique; the median radiation dose was 6000 cGy, with more than 95% of patients receiving at least 4500 cGy. In addition, seven patients received postoperative chemotherapy. The 5-year overall survival rate was 62%, disease-free survival 64%, local control 68%, and freedom-from-distant metastasis 85%. Thirteen patients had local recurrences, with greater than 75% recurring within 3 years. Sites of local recurrence were as follows: trunk (3), pelvis (3), lower extremities (4), and head and neck (3). There appears to be a correlation of local failure with positive surgical margin: of 23 patients with positive margins, 9 (39%) had local recurrences, whereas 1 of 11 patients (9%) with negative margins had local recurrence. Three of 13 patients with persistent or recurrent disease were salvaged by additional treatment, rendering ultimate local control in 80% (39/49). Thirty-four of 36 patients with local control obtained good to excellent function. Two patients were found to have grade 3 complications: 1 patient had edema of the extremity, and the other developed necrotic skin ulcer that was successfully treated with hyperbaric oxygen. Five patients developed distant metastases, with 80% occurring within 2 years. In summary, adequate but conservative surgery with postoperative radiotherapy for malignant fibrous histiocytoma can achieve local tumor control as well as preservation of functional limbs with acceptable morbidity in a large proportion of patients.

Radiation therapy for stage i and iia testicular seminoma

PURPOSE To review the survival, cure rate, treatment morbidity, and late sequelae of histologically confirmed seminoma patients who underwent orchiectomy and radiation therapy at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, from 1964 to 1988. METHODS AND MATERIALS There were 128 patients, with a median patient age of 37 years (range, 17-79 years). Follow-up ranged from 1-24 years, with a median of 6.7 years. There were 95 patients with Stage I and 33 with Stage IIA disease. All patients were treated with orchiectomy followed by iliac and paraaortic irradiation (median tumor dose: 2500 cGy for Stage I and 3400 cGy for Stage IIA patients). Twenty-five of 33 patients with Stage IIA disease received prophylactic mediastinal and left supraclavicular irradiation (median dose, 2700 cGy). RESULTS For patients with Stage I disease, 5-year disease-free survival, overall survival, and survival corrected for intercurrent disease were 97%, 100%, and 100%, respectively. For patients with Stage IIA disease, the 5-year disease-free survival, overall survival, and survival corrected for intercurrent disease were 93%, 89%, and 97%, respectively. Four patients (3%) had recurrences; all were outside the radiation treatment field. Three of four were successfully salvaged with chemotherapy and rendered disease-free; the other patient refused treatment. There were no mediastinal recurrences whether prophylactic mediastinal irradiation was administered or not. Bowel obstruction and necrosis developed in one patient who received 3363 cGy midplane dose to the pelvic and paraaortic areas as well as additional intraperitoneal colloidal 198Au (150 mCi) for a ruptured seminoma from an undescended testis. CONCLUSION In summary, radical orchiectomy and irradiation of the iliac and paraaortic lymphatics is the treatment of choice for patients with Stage I and IIA testicular seminoma.

Combined hyperthermia and irradiation in the treatment of superficial tumors: results of a prospective randomized trial of hyperthermia fractionation (1/wk vs 2/wk)☆

From December 1984 to December 1989, 240 superficially located recurrent/metastatic malignant lesions (173 patients) were enrolled in a prospective randomized study of one versus two hyperthermia fractions per week. In the majority of patients, the dose of radiation therapy was less than 4000 cGy over 4 to 5 weeks. Stratification was by tumor size, site, and histology. The goal of the hyperthermia sessions were 42.5 degrees C for 45-60 min minimum intra-tumor measured temperature. Hyperthermia was given after radiation within 30-60 min. External applicators, both microwave (over 90% of treatments) and ultrasound, were used. Overall, complete response rate in 222 evaluable lesions was 56.3% (125/222) with a minimum follow-up of 6 months and a maximum follow-up of 52 months. The complete response rate for once a week versus twice a week hyperthermia group was 54.7% and 57.8%, respectively. The severe complication rate was 18% (41/222). There was no difference between the two treatment arms. Cox regression analyses were performed to study the prognostic significance of patient characteristics, tumor characteristics, and treatment parameters. Detailed analysis and results are presented.

Analysis of prognostic factors in localized gastric lymphoma: The importance of bulk of disease

PURPOSE To identify prognostic factors in localized gastric lymphoma patients for optimal therapy selection. METHODS AND MATERIALS From 1974 to 1990, 77 patients with localized gastric lymphoma (38 Stage IE and 39 Stage IIE) were treated with radiation therapy, chemotherapy, surgery, or a combination. Univariate and multivariate local control and survival analyses were performed on possible prognostic factors, such as patient age, gender, histologic subtype, stage, tumor size, depth of penetration, multicentricity, and treatment modality. RESULTS At 5 years, the relapse-free survival was 52%; 74% of the relapses occurred at local sites. Smaller tumor size was most strongly associated with local control (p = .001) and relapse-free survival (p < .001). Patients with tumor sizes < or = 5 cm had relapse-free survival of 87%, compared with 41% and 15% for those with tumor sizes of 5.1 cm to 10 cm and > 10 cm, respectively. The 47 patients who received combined-modality therapy had a relapse-free survival of 65%, compared with 24% for the 30 who received single-modality therapy (p < .01). Although patient age, stage, depth of penetration, and resective surgery affected the above endpoints, these factors were not independent predictors of outcome. Analysis of treatment subgroups showed that surgical resection combined with postoperative irradiation was associated with highest local control (p = .002) and the best relapse-free survival (p = .004), when compared with other treatment modalities. In 27 patients with tumor sizes < or = 5 cm, comparison of the 15 patients who had surgery with the 12 who did not failed to reveal a local control benefit from the addition of surgery. CONCLUSION These data demonstrate that tumor bulk is an important prognostic determinant of local control and relapse-free survival in localized gastric lymphoma patients. Stage IE and IIE lymphoma of the stomach can be selectively treated with primary radiation, but surgical resection may be necessary for large tumors (> 5 cm), followed by adjuvant radiation.

Carcinoma of the rectum

BACKGROUND: Preoperative radiation therapy can markedly improve local control of rectal carcinoma. However, some tumors do not respond well to moderate doses of preoperative radiation and would be better served by more aggressive preoperative treatment (e.g., chemoradiotherapy). Cellular predictors of responsiveness to radiation can help to select lesions for more aggressive treatment. In addition, there is a need for cellular predictors of metastatic potential. This is particularly important in the setting of preoperative radiation—downstaging by preoperative treatment can obscure the true pathologic stage of a tumor and confound the usual selection criteria for postoperative chemotherapy. PURPOSE: This study was undertaken to determine if proliferating cell nuclear antigen (PCNA), p53, DNA ploidy, and S-phase fraction are associated with response to radiation and/or risk for distant metastatic disease and to determine if these cellular markers are best evaluated from preradiation biopsy specimen or the larger (but possibly altered) final surgical specimen. MATERIALS AND METHODS: Archival specimens from 23 cases of ultrasound T3 or T4 rectal carcinoma treated preoperatively with radiation therapy were reviewed. Eligible lesions had preradiation biopsy specimens of sufficient size for flow cytometric review of archival tissue. Factors considered included PCNA positivity, presence of mutant nuclear p53, more than 30 percent tumor cells in S-phase, and presence of aneuploidy. RESULTS: With a median follow-up of three years, overall freedom from relapse was 83 percent, with all but one failure being extrapelvic. PCNA positivity in the preradiation specimen was significantly (P=0.025) associated with a greater risk of tumor recurrence. In addition, there was a trend to greater likelihood of “probable downstaging” (defined as surgical T stage less than preradiation ultrasound T stage) for lesions that were PCNA-negative or lesions with normal p53. Biomarkers measured in the postradiation surgical specimen were not associated with either freedom from relapse or response to radiation. Radiation treatment appeared to produce false-negatives in the final specimen. Thus, there were significantly more specimens converting from PCNA-positive to PCNA-negative after preoperative radiation than would be expected solely on the basis of sampling errors (P=0.004). Similar results were found for abnormal p53 findings (P=0.02). CONCLUSIONS: Prospective studies of biomarkers should be based on pretreatment specimens if preoperative radiation is given. For carcinoma of the rectum, PCNA and p53 may be useful predictors of both metastatic potential and responsiveness to radiation.

Cure of early-stage Hodgkin's disease with subtotal nodal irradiation

Ninety‐four consecutive patients with Stage I or II Hodgkins disease who presented supradiaphragmatically were treated with radiation therapy alone at the Mallinckrodt Institute of Radiology from January 1978 through December 1986. Fifty‐two patients (55%) were staged pathologically, and 42 (45%) were staged clinically. The latter included lymphangiography and/or abdominal computed tomographic scan. Most patients with B symptoms and/or bulky disease were excluded from this series. Seventy‐four patients were treated with subtotal nodal irradiation (mantle and periaortic fields). The spleen was treated if the patient had not undergone splenectomy. Twenty patients received mantle irradiation only. No patient received total nodal irradiation. All patients had an initial complete response. With a minimum follow‐up of 7 months (median, 7.7 years; seven patients died before 3 years of follow‐up, but all other patients had at least 3 years of follow‐up), 81 patients (86%) remained disease‐free. Six of 52 (12%) of the pathologically staged group had a relapse, as did seven of 42 (17%) of the clinically staged group (P = 0.68). Eight of 57 Stage I patients versus five of 37 Stage II patients had a relapse (P > 0.99). Analysis of disease‐free survival by age, histologic findings, sex, and sites of involvement did not predict relapse. The pelvis was the most common site of failure (nine patients, 10%). However, only three patients (3%) failed in the pelvis alone. These results indicate that patients who, after adequate clinical staging with selective use of staging laparotomy, are found to have Stage I and II Hodgkins disease may be treated with subtotal nodal irradiation with a high rate of cure.