Chimeric rabies SADB19-VSVg-pseudotyped lentiviral vectors mediate long-range retrograde transduction from the mouse spinal cord.

Lentiviral vectors have proved an effective method to deliver transgenes into the brain; however, they are often hampered by a lack of spread from the site of injection. Modifying the viral envelope with a portion of a rabies envelope glycoprotein can enhance spread in the brain by using long-range axon projections to facilitate retrograde transport. In this study, we generated two chimeric envelopes containing the extra-virion and transmembrane domain of rabies SADB19 or CVS-N2c with the intra-virion domain of vesicular stomatitis virus. Viral particles were packaged containing a green fluorescent protein reporter construct under the control of the phosphoglycerokinase promoter. Both vectors produced high-titer particles with successful integration of the glycoproteins into the particle envelope and significant transduction of neurons in vitro. Injection of the SADB19 chimeric viral vector into the lumbar spinal cord of adult mice mediated a strong preference for gene transfer to local neurons and axonal terminals, with retrograde transport to neurons in the brainstem, hypothalamus and cerebral cortex. Development of this vector provides a useful means to reliably target select populations of neurons by retrograde targeting.

Guidelines for radiotherapeutic techniques for cervical metastases from an unknown primary.

Between 1968 and 1980, radiotherapy was part of the treatment of 120 patients with cervical nodes from an unknown primary tumor. Thirteen patients presented with supraclavicular nodes only and 14 presented with massive adenopathy; they are analyzed separately. The remaining 93 patients are analyzed in this report with emphasis on the applied radiotherapeutic techniques. Twenty of the 93 patients received radiation treatment to the neck only, 26 to the naso- and oropharynx and neck, and 47 to the naso-, oro-, and hypopharynx and neck. Fourteen patients subsequently developed a tumor at a primary site or a recurrence of metastases in the neck; in nine patients the disease recurrence was in areas that had not been irradiated. There was an increase in failures above the clavicles in patients who received irradiation to the neck alone. No correlation was found between initial tumor staging and subsequent failure, nor between types of surgical procedures and failure. In 86 of 93 (92.5%) patients there was eventual control of disease above the clavicles; 22 of the 93 patients died of disease, whereas 36 died of other causes. The determinate survival rate for the 93 patients treated with curative intent is 70% at 10 years. Guidelines for selection of techniques based on tumor and patient factors are discussed.

Time course and incidence of late complications in patients treated with radiation therapy for FIGO stage IB carcinoma of the uterine cervix.

PURPOSE: To determine the time course and incidence of late complications from radiation therapy in patients treated with radiation for FIGO Stage IB carcinoma of the uterine cervix, and to evaluate patient and tumor factors associated with an increased probability of treatment complications. METHODS AND MATERIALS: The medical records of 1784 patients with FIGO Stage IB cervical carcinoma who were treated with initial radiation therapy between 1960 and 1989 were retrospectively reviewed. Follow-up was obtained from clinic visits and correspondence with patients and their physicians. Treatment complications were graded retrospectively. Complication rates were calculated actuarially; patients who died of disease or intercurrent illness without experiencing a major complication were censored at the time of death. There were 1241, 924, 548, and 274 patients followed for more than 5, 10, 15, and 20 years, respectively. RESULTS: Of patients treated for Stage IB cervical carcinoma, 7.7% and 9.3% had experienced major (> or = Grade 3) complications at 3 and 5 years, respectively. After 5 years, there was a small but continuous risk of approximately 0.34% per year, resulting in an overall actuarial risk of having had major complications of 14.4% at 20 years. The risk of developing major urinary tract complications was approximately 0.7% per year for the first 3 years of follow-up, decreasing to about 0.25% per year for at least 25 years. In contrast, the risk of developing rectal complications was about 1% per year during the first 2 years, with a subsequent sharp decline to about 0.06% per year between Years 2 and 25. The risk of fistula formation was approximately doubled in the 234 patients who underwent adjuvant extrafascial hysterectomy (5.3 vs. 2.6% at 20 years; p = 0.04) and in the 111 patients who had pretreatment laparotomy (5.2 vs. 2.9%; p = 0.007). The risk of developing small bowel obstruction was increased in patients who underwent pretreatment laparotomy (14.5 vs. 3.7% at 10 years; p < 0.0001) and in patients who weighed < 120 pounds (8.2 vs. 3.6%; p = 0.004), but was not increased in patients who underwent adjuvant hysterectomy. A significantly greater risk of gastrointestinal complications was observed in black and non-Hispanic white patients than in Hispanic women (p = 0.01), even though there was no difference in the rate of developing urinary tract complications (p = 1.0). There was no correlation between the actuarial risk of developing major complications and the patients' age at the time of treatment, but the cumulative risk was greater for patients who were treated at a young age because these patients were more likely to survive to be exposed to a very long period of risk. CONCLUSIONS: Using techniques described by Fletcher and Delclos, the risk of major complications from aggressive irradiation for Stage IB carcinoma of the cervix is low and does not warrant compromises in the intensity of treatment that might decrease the high cure rates achieved in such patients. The long time course of some late complications also suggests that continued surveillance of survivors, by physicians experienced in the diagnosis and management of the sequelae of the curative radiation treatment of cervical cancer, is important.

Long-range results for breast cancer patients treated by radical mastectomy and postoperative radiation without adjuvant chemotherapy: an update.

Between 1963 and 1977, 941 patients with carcinoma of the breast received, at the University of Texas M.D. Anderson Cancer Center, peripheral lymphatic irradiation alone or with chest wall irradiation after a radical or modified radical mastectomy. None of the patients received adjuvant chemotherapy. The incidence of patients with histologically involved axillary nodes was 70%. The lymphatics of the apex of the axilla, of the supraclavicular area, and of the internal mammary chain were irradiated in patients with histologically positive axillary nodes and/or in patients with central or inner quadrant primaries regardless of the axillary status. When in 1963 an electron beam became available, chest wall irradiation has been added to the peripheral lymphatics irradiation, primarily when there was a heavy infestation of the axillary nodes. The disease-free survival curves tend to flatten out at 10 years. At 10 and 20 years, the disease-free survival rates are respectively 55% and 50% for all patients, 44% and 40% for all patients with positive nodes, 56% and 48% for the patients with one to three positive nodes, and 33% and 30% for the patients with four or more positive nodes. The comparison of the mortality curves between the general population and the breast cancer patients seems to indicate a cured fraction, since the curves become parallel at 17 years. The highest incidence of failures is between 0 and 5 years, still a significant incidence between 5 and 10 years, but after 10 years the incidence of failures is relatively small.

Comparison of surgery and radiation therapy for non-small cell carcinoma of the lung with mediastinal metastasis.

Interest in the potential role of induction chemotherapy for patients with marginally operable non-small cell carcinoma of the lung (NSCCL) led to a retrospective study of surgical resection and radiation therapy, alone or combined with each other and/or chemotherapy. All 169 patients seen at The University of Texas M. D. Anderson Cancer Center from 1980 through 1985 with evidence of NSCCL metastatic to ipsilateral mediastinal lymph nodes but without extrathoracic spread were evaluated (NSM0). All patients had histologic or cytologic confirmation of NSCCL and clinical or pathologic evidence of mediastinal involvement. Nine patients received CHM alone and were excluded. The male:female ratio was 3:1, and 50% were less than 60 years old. Squamous cell carcinoma was reported in 42%, adenocarcinoma in 45%, large-cell carcinoma in 9%, and unclassified carcinoma in 4%. Radiation therapy (RT) was selected for 81 patients (+ CHM in 56%), in 85% because of the extent of tumor involvement and in 15 for medical reasons. Of RT patients, 31% had a Karnofsky performance status (KPS) of less than or equal to 80, 30% had greater than 5% weight loss, and 9% had Stage IIIB disease. Surgical resection (SX) was used in 41 patients (+CHM in 41%), of whom 10% had KPS less than or equal to 80, 17% had greater than 5% weight loss, and 2% had Stage IIIB disease. SX + RT was the treatment for 38 patients (+ CHM in 36%), of whom 13% had KPS less than or equal to 80, 13% had greater than 5% weight loss, and 13% had Stage IIIB disease. The proportions of patients with KPS less than or equal to 80 and weight loss greater than 5% were significantly greater (p less than .01 and p less than .05, respectively) in the RT group than in the other treatment groups. Actuarial survival rates at 2 and 5 years were 24% and 9%, respectively, for RT, 32% and 17% for SX, and 46% and 25% for SX + RT. Overall survival rates for all 160 patients were 30% at 2 years and 14% at 5 years. Prognostic factors that were found to be important were KPS (p = .027) and weight loss (p = .001); age, sex, histology, and Stage IIIa versus IIIB disease were not significantly related to outcome. The results of treatment with SX + RT were significantly better than with RT alone (p = .03); the difference between RT alone and SX alone was not significant (p = .39).(ABSTRACT TRUNCATED AT 400 WORDS)

The role of serum prostatic acid phosphatase in the management of adenocarcinoma of the prostate with radiotherapy.

Between 1974 and 1983, 472 patients with clinically-staged adenocarcinoma of the prostate treated by radiotherapy had baseline and follow-up prostatic acid phosphatase (SPAP) measurements by the enzymatic Roy method. The mean pretreatment SPAP was higher in Stage C (0.65 mIU/ml) than in combined Stages A2/B (0.43 mIU/ml), (p less than 0.05). Likewise, the incidence of elevated SPAP (greater than 0.8 mIU/ml) was also higher in Stage C (12%) than in Stages A2/B (3%), (p less than 0.01). Only 3 of 113 patients in Stages A2/B had an elevated SPAP and all three remain disease-free. In Stage C elevated SPAP was an adverse prognostic factor, and patients with a normal SPAP fared worse if their value was in the upper half of normal (greater than 0.4 mIU/ml) rather than in the lower half (less than or equal to 0.4 mIU/ml). However, in Stage C, tumor grade was found to correlate with initial SPAP, so that the higher the grade, the higher was the mean SPAP and the greater was the incidence of elevated SPAP. When stratified for grade, the prognostic significance of low-normal versus high-normal SPAP in Stage C was lost. An elevated SPAP was, however, an independent adverse prognostic factor for patients with intermediate and high grade tumors. Following radiotherapy, mean SPAP values fell significantly within 1-3 months. For patients with initially normal SPAP, this fall was of no prognostic significance. In 80% of the patients with baseline elevation of SPAP, the values normalized following treatment and the relapse rate in these patients was 51%, which was still higher than the relapse rate of patients with initially normal SPAP (33%) (p less than 0.05) but was lower than the 89% relapse rate in patients whose postradiation SPAP did not normalize (p less than 0.05). Pretreatment SPAP was of independent prognostic significance for only 6% of the study population and therefore has quite limited usefulness in the management of this disease. SPAP decreases following radiotherapy, but this is of prognostic significance only for the small group of patients with elevated pretreatment values.

The influence of tumor size and morphology on the outcome of patients with FIGO stage IB squamous cell carcinoma of the uterine cervix.

PURPOSE: To define the influence of tumor size and morphology on rates of central tumor control (CTC), pelvic tumor control (PTC), and disease-specific survival (DSS) in patients treated with radiotherapy for squamous cell carcinoma of the intact uterine cervix. METHODS AND MATERIALS: Records of 1526 patients treated with radiotherapy for FIGO Stage IB squamous cell carcinoma of the intact uterine cervix between 1960 and 1989 were retrospectively reviewed. The maximum tumor or cervical diameter was determined from clinical descriptions for 1494 patients. Tumors were divided into nine size categories. Tumors > or = 4 cm were further classified according to the dominant morphology (i.e., exophytic or endocervical). Median follow-up was 12.2 years. Five-year CTC, PTC, and DSS rates were calculated actuarially. RESULTS: CTC, PTC, and DSS rates correlated strongly with tumor diameter (p < 0.0001). Overall, CTC, PTC, and DSS rates for patients with tumors < 5 cm were 99%, 97%, and 88%, respectively. For patients with tumors 5-7.9 cm these rates were 93%, 84%, and 69%, respectively. There were no significant differences in the rates of PTC, CTC, or DSS between subgroups of patients with lesions 5-7.9 cm in diameter. The rates of CTC (97%) and DSS (76%) for patients with 5-7.9 cm exophytic tumors were significantly better than those for patients with endocervical tumors of the same size (91% and 66%, respectively); there was no difference in the PTC rate. CONCLUSION: Although the CTC rates were excellent for all patients with tumors < 8 cm in diameter, these rates for tumors < 5 cm (99%) and for exophytic tumors 5-7.9 cm (97%) make it difficult to justify the use of adjuvant hysterectomy. Although patients with tumors of 5-7.9 cm had consistently poorer PTC and DSS rates than did patients with smaller tumors, the control rates achieved with aggressive radiotherapy were still excellent. The strong correlation between tumor size and outcome suggests that tumor diameter should be assessed when tumors are clinically evaluated and staged and when treatment results are reported for patients with FIGO Stage IB carcinoma of the uterine cervix.

Prognostic implications of age in breast cancer patients treated with tumorectomy and irradiation or with mastectomy.

Conservation breast treatment is of particular interest to young women, but whether saving the breast carries a penalty in shorter survival or local-regional recurrent disease has not been well-established. At The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston, 1161 patients treated prior to 1983 with Stage I or II breast cancer were reviewed. Of these patients, 378 were treated with tumorectomy plus irradiation, and 783 were treated with radical or modified radical mastectomy. The two patient groups were compared relative to local-regional disease recurrence and overall and disease-free survivals. Local recurrences in the breast appear to be more frequent in patients less than or equal to 35 years of age treated with tumorectomy and irradiation than in patients older than 35 years, but in patients aged less than or equal to 50 or greater than 50 or less than or equal to 35 or greater than 35 years, there was no significant statistical difference between tumorectomy and irradiation or mastectomy nor was there a difference in disease-free survival. Overall survival rates favored patients treated by tumorectomy and irradiation.

The role of radiation therapy in stages A2 and B adenocarcinoma of the prostate.

Between 1965 and 1982 definitive external beam radiation therapy was given to 114 patients with clinically Staged A2 (32 patients) and B (82 patients) adenocarcinoma of the prostate. These patients were not considered to be surgical candidates because of age, comorbidity or disease extent, or because they had refused surgery. Total prostatic doses ranged from 60 to 70 Gy. For 90 surviving patients, follow-up duration ranged from 32 to 188 months with a median of 5 years. The 5- and 10-year uncorrected survival rates for all patients, which were 89% and 68% respectively, were no different from the survival expectation of age-matched men in the general population. Disease-free survival rates at the same time periods were 89% and 86%. There were no significant differences in disease-free survival between Stage A2 and Stage B. Four patients (3.5%) developed local recurrence. Bone metastases, which occurred in 9 of 11 treatment failures were the predominant cause of failure. An analysis of 11 potential prognostic factors was fruitless. Pelvic node irradiation did not improve the outcome. The incidence of complications was acceptable. Anorectal problems developed in 20% of patients and urinary manifestations occurred in 20%, and only 2 patients (1.8%) developed serious problems. We concluded that localized external beam high-energy radiation therapy provides excellent local control for disease limited to the prostate, with survival rates that rival those of radical surgery.

Safety of adjunctive transvaginal beam therapy in the treatment of squamous cell carcinoma of the uterine cervix.

At The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston between 1970 and 1980, 159 patients with bulky cervical cancers of FIGO Stages IB or II were treated with transvaginal orthovoltage radiotherapy (TVR) as an adjunct to standard external beam megavoltage irradiation and brachytherapy. The majority received 10 or 15 Gy air dose in 2-3 fractions using 125-250 kVp X rays. The dose from TVR was ignored in subsequent standard treatment planning. The absolute 5-year local control and survival rates were 82 and 83%, respectively. A total of 9 patients (5.7%) developed serious treatment complications that were significantly related to performance of a staging lymphadenectomy prior to radiotherapy and to an external beam pelvic dose of 50 +/- 0.5 Gy versus 40 +/- 0.5 Gy. The risk complications was not related to the dose of TVR or brachytherapy within the ranges used. Provided patients are properly selected and appropriate technical precautions are exercised, TVR is a safe technique. It is effective in controlling bleeding and shrinking large exophytic tumors, and very likely contributes to improved tumor control by facilitating optimal geometry for intracavitary therapy.

Postoperative adjuvant radiotherapy for adenocarcinoma of the rectum and rectosigmoid.

One hundred five patients treated with potentially curative surgery and adjuvant postoperative radiotherapy for adenocarcinoma of the rectum and rectosigmoid from 1973 through 1981 were reviewed. Radiation therapy was given with 18-25 MeV X rays in doses of 40-50 Gy in 5 weeks (midline dose) using AP-PA fields in 97 patients. A boost of 6 to 10 Gy was directed to the area of maximum risk by anterior-posterior or perineal fields in 71 patients. Local failure occurred in 15 patients and was documented pathologically in 8 patients, or clinically or radiologically in 7 patients. The local recurrences according to the Modified Astler-Coller staging criteria were: B1: 0% (0/3); B2: 4% (1/24); B3: 31% (4/13); C1: 8% (1/12); C2: 18% (8/45); C3: 20% (1/5). Local failure after adjuvant radiotherapy versus surgery alone was compared. The comparison of local failure of combined treatment versus surgery alone, from our institution, is as follows: B2-4% vs 13%, B3-31% vs 26%, C2-18% vs 30%, and C3-20% vs 49%. Sixty-one patients (58.1%) have been followed for 5 years, with a median of 73 months and a minimum of 24 months. The actuarial 5-year survival (disease-free) for the entire group is 55% and is not statistically different for the groups with negative or positive nodes. Fourteen patients (13%) required surgery for small bowel complications; four others (4%) had symptomatic small bowel obstruction treated with conservative therapy only. Small bowel obstruction occurred in 4 of 16 (25%) treated with radiation fields above L5, whereas those treated below L5 had an 11% incidence. Postoperative adjuvant radiotherapy can increase local tumor control compared to surgery alone. The small bowel complication rate in this series most likely reflects AP-PA treatment technique and can be decreased by the use of multiple fields with maximum shielding of the small intestine.

Treatment of endometrial carcinoma with radiation therapy alone.

PURPOSE: To review the results of treatment with radiotherapy alone in 152 patients with adenocarcinoma of the endometrium who had medical or surgical contraindications to hysterectomy. METHODS AND MATERIALS: We reviewed the records of all patients who were treated with radiotherapy alone for uterine carcinoma at The University of Texas M. D. Anderson Cancer Center between 1960 and 1986. One hundred fifty-two cases were analyzed. Most patients had multiple medical problems. One hundred sixteen patients were treated with intracavitary radiotherapy alone. A combination of external beam and intracavitary radiotherapy was used for 10 patients with Stage I disease who had unusually large cavities, 10 patients with Stage II disease, and 13 of 15 patients with Stage III or IV disease. Histologic material was reviewed in 91 cases. RESULTS: Ten years after treatment, these patients were twice as likely to have died of intercurrent illness as of uterine cancer. The 5-year disease-specific survival rate of patients with Stage I disease was 87%. The disease-specific survival of patients with Stage II disease was 88%, which was not significantly different from that of Stage I patients. Stage III and IV patients had a significantly poorer disease-specific survival rate of 49% at 5 years. Intrauterine recurrence occurred in 14% of the patients with Stage I or II disease. Salvage treatment was attempted in 5 of the 10 patients who had isolated intrauterine recurrences of Stage I disease and was successful in all cases. Extrauterine pelvic recurrence developed in only 3% of Stage I and II patients. Of 82 Stage I and II carcinomas that were available for pathologic review, 17 (21%) were clear-cell or papillary serous variants. The disease-specific survival rate of patients with Stage I or II papillary serous carcinomas was 43%, significantly poorer than that of patients with endometrioid carcinomas. Seven patients experienced acute anesthesia-related complications; none were fatal. Five patients had serious late complications of radiation therapy. CONCLUSION: Radical radiotherapy achieved acceptable DSS and local control rates in patients with medically or surgically inoperable uterine carcinoma. However for patients with localized disease, such treatment is justified only when the operative risk exceeds the 10-15% uterine recurrence rate expected with radiation alone.

Acute and late toxicity associated with sequential bleomycin-containing chemotherapy regimens and radiation therapy in the treatment of carcinoma of the nasopharynx.

Between 1975 and 1984, 33 patients with squamous cell carcinoma of the nasopharynx received adjuvant chemotherapy before and/or after definitive radiotherapy at UT M. D. Anderson Hospital. The favored chemotherapy regimens during this time were BCMF (bleomycin, cyclophosphamide, methotrexate, and 5-FU) and PMB (cisplatinum, methotrexate, and bleomycin). Total radiation doses to the primary site averaged 65 Gy for T1 and T2 lesions and 70 Gy for T3 and T4 lesions. Neck nodes were given boost treatments to a maximum of 70 Gy, depending on the extent of the disease. The outcome of treatment in these patients was compared to that of a stage-matched group of 71 patients treated during the same time period with radiotherapy alone. However, the groups were not matched with regard to histologic subtypes: 45% of the radiation-only group had prognostically unfavorable keratinizing squamous carcinomas (WHO 1) compared with 18% of the combined modality group. Overall disease-free survival at 5 years was 63% in the combined modality group and 44% in the radiation only group (p = 0.15). Both acute reactions and late treatment complications were much more frequent and severe in patients receiving combined modality treatment. In patients treated with chemotherapy prior to radiation therapy, 10/20 (50%) experienced severe acute toxicity (RTOG Grade 3 or 4) versus 9/71 (13%) in the radiotherapy-only group. Severe late normal tissue injury occurred in 15/33 (45%) of the combined modality group versus 5/71 (7.0%) in the control group. The majority of the late complications in the adjuvant chemotherapy group consisted of severe soft tissue and muscle fibrosis. The average total bleomycin dose in the patients with severe late soft tissue and muscle fibrosis was 336 mg. The actuarial risk of developing a severe late complication by 2 years after treatment was 68% in the combined modality group versus 8% in the radiation-therapy-only group (p = .001). The probability of remaining both disease-free and complication-free at 5 years was 40% in the radiation-only group and 22% in the combined-modality group (p = 0.08). Comparison of these results with other published reports emphasizes the importance of late toxicity data in assessing the ultimate value of combined modality therapy.

Postoperative irradiation in malignant epithelial tumors of the parotid.

From 1954 through 1979, 77 patients with malignant tumors of the parotid gland were referred from the Department of Head and Neck Surgery for postoperative irradiation. The analysis has been made by grouping the patients according to the estimated amount of disease left after the surgical procedure and by the histological types. There were no local failures in the low-grade tumors, and there were 6 in the 63 patients with high-grade tumors. With gross residual disease or potential residual disease the patients received slightly higher doses than those without. Although there were only 6 failures in the various histological types, there was perhaps a trend to more failures in the adenocarcinomas. There was no difference in the failure rates in patients having had a total resection of the facial nerve or partial resection or no resection. The preferred treatment has been a combination of 20 MeV photons and 18 MeV electrons. Five neck failures were essentially a result of lack of elective irradiation of the neck. Severe complications appeared only in the patients irradiated either for gross residual disease or excision of a recurrence with a high risk of widespread microscopic residual disease.

Desmoid tumors: a 20-year radiotherapy experience.

From 1964 through 1984, 45 patients were referred for radiation therapy for desmoid tumor. Fourteen patients had inoperable lesions, or gross residual disease after incomplete resection. Thirty-one patients received postoperative XRT for positive margins or concern about the adequacy of the margin. The minimum follow-up was 2 years, maximum 22 years, median 7.6 years. No patient was lost to follow-up. The primary site was head and neck in 5, upper extremity in 10, chest wall and back in 8, abdomen 2, pelvis 4, and lower extremity 16. All patients were treated with megavoltage radiation therapy using shrinking field techniques. Large fields received a median dose of 50 Gy in 25 fractions. Boost fields were used in the majority of patients to deliver an additional dose of 7 to 27 Gy. The range of total doses was 50 to 76.2 Gy. Three patients received a boost with neutrons. Analysis of patients with inoperable or gross residual showed tumor control in 10 of 14 with a median follow-up of 9.4 years. Resolution of gross disease occurred at a range of 1/2 to 64.3 months with a median of 9 months. There was no evidence of a higher probability of ultimate control at higher doses. Tumor control was equal for men and women. The ten patients with local control had doses from 50 to 76.2 Gy whereas the four patients with in field failures had tumor doses of 57 to 66.4 Gy. There was no difference in median dose for patients with local control (60.3 Gy) versus those with tumor recurrence (60 Gy). For subclinical disease, 31 patients receiving postoperative or preoperative XRT had a 77 percent probability of local control in spite of the history of multiple tumor recurrences; local control was achieved in 8 of 9 with negative or uncertain margins and 16 of 22 with positive margins. An analysis of local control as a function of the number of operations revealed that patients referred for adjuvant radiotherapy with no more than two operative procedures had an 88 percent probability of local control, versus 66 percent for more than two operative procedures. All grade 3 complications (defined as requiring surgical intervention or prolonged hospitalization) occurred with doses above 60 Gy. Management of recurrences was successful in 8 of the 11 patients and no patient has died of tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

The role of limited surgery with irradiation in primary treatment of ductal in situ breast cancer.

The results of management of ductal carcinoma in situ with limited surgery and radiotherapy are presented at a median follow-up of 92 months. In 44 treated breasts the actuarial 10-year loco-regional control rate was 91%, four patients having recurred. Each loco-regional failure was due to invasive carcinoma and three of the affected patients have developed metastases. No patient developed metastases without previous clinically-evident invasive loco-regional disease. The 10-year disease-specific survival rate was 96%. Previous publications have shown that the 25% or greater risk of local failure after limited excision of ductal carcinoma in situ can be reduced by irradiation of the breast. Our results demonstrate that good loco-regional control is maintained in the longer term.

The relationship between brachytherapy dose and outcome in patients with bulky endocervical tumors treated with radiation alone.

PURPOSE: To evaluate the relationship between brachytherapy dose and outcome in patients treated with external radiotherapy (40 Gy to the whole pelvis) and intracavitary radium therapy for bulky endocervical tumors. METHODS AND MATERIALS: Between 1962 and 1985, 98 patients with Stage IB-IIB bulky endocervical carcinomas (> or = 6 cm in diameter) treated with radiotherapy alone received 40 Gy to the whole pelvis followed by 2 or more intracavitary treatments. Twenty-five patients received < 6000 mg-hr of intracavitary treatment and 73 received > or = 6000 mg-hr (an average dose to point A of approximately 49 Gy). Brachytherapy exposures ranged from 4800-7885 mg-hrs. RESULTS: Patients who received < 6000 mg-hr tended to have unfavorable (narrow) vaginal anatomy (p < 0.01) and to be treated in the later years of the study (p < 0.01). The high-dose group included a somewhat greater proportion of patients with positive lymphangiograms or poor responses to initial external beam treatment. Despite having somewhat more favorable tumors, patients who received less than 6000 mg-hr had a higher rate of pelvic disease recurrence at 5 years (33%) than those who received higher doses (16%) (p = 0.03). Actuarial survival rates at 5 years were 44% and 60% for the low- and high-dose groups, respectively (p = 0.14). Among those who received more than 6000 mg-hr, there was no significant relationship between brachytherapy dose and pelvic disease control. Calculated actuarially, the rate of major (> or = grade 3) complications at 5 years was 23% in the low-dose group and 10% in the high-dose group (p = 0.1). CONCLUSIONS: The relatively high incidence of pelvic disease recurrence and complications in patients who receive less than 6000 mg-hr reflects the narrow therapeutic window for complication-free pelvic disease control in patients with bulky central disease and unfavorable normal tissue anatomy. The results also demonstrate a high pelvic control rate and acceptable morbidity in patients with favorable anatomy treated with high-dose radiotherapy alone.

Relationship between lymph nodal status and primary tumor control probability in tumors of the supraglottic larynx.

A retrospective review of 248 patients with squamous cell carcinoma of the supraglottic larynx was undertaken to determine the relationship between the probability of control of the primary lesion, the extent of neck nodal disease at initial presentation, and its ultimate control. All patients were treated at the U.T. M. D. Anderson Hospital between 1960 and 1980, and had a minimum of 3 years follow-up. The primary lesion was staged T1 in 38 patients, T2 in 132, T3 in 50 and T4 in 28. The initial volume of neck nodal disease was scored on a scale of 0 (no palpable nodes) to 9 (bilateral neck nodes greater than 6 cm in diameter). All primary lesions were treated definitively with megavoltage radiation therapy. Treatment to the neck varied according to the extent of lymph node involvement. There was no significant difference in the range of total radiation doses delivered to the primary lesion, stage for stage, in patients who presented with clinically negative or positive nodes, or in those with controlled versus uncontrolled neck disease. Analysis of the probability of primary tumor control was made by life table methods because of the poorer survival expectation in node positive patients. For T1 and T2 primary lesions, any positive node decreased the probability of primary tumor control (p = 0.06). For T3 and T4 lesions, a single node less than 3 cm in diameter did not worsen the chance of primary tumor control, but any greater degree of lymph node involvement did (p = 0.03). For both T stage groupings, the probability of primary tumor control at 5 years decreased progressively with increasing neck nodal disease. Primary tumor control probability was also significantly associated with control of the neck disease, independent of the modality of neck treatment. No correlation could be demonstrated between the histological grade of the primary tumor and initial lymph node status or tumor control probability. Possible interpretations of this manifestation of biological heterogeneity are discussed.

Radiation therapy following resection of non-small cell bronchogenic carcinoma.

Between 1970 and 1982, 102 patients received postoperative radiotherapy after attempted curative resection of bronchogenic carcinoma at The University of Texas M. D. Anderson Cancer Center. Surviving patients had a minimum follow-up of 3 years. Eight patients had pathological Stage I disease, 29 Stage II, and 65 Stage III. The 5-year actuarial survivals for patients with stages I, II, and III disease were 83%, 55%, and 38%, respectively (p = .04). Corresponding values for patients with N0, N1, and N2 disease were 74%, 56%, and 28% (p = .01). No significant differences in survival were seen based on T stage or tumor histology. Nine patients had gross residual disease following surgery, and 19 had microscopic residual disease. The 5-year actuarial survival was 78% for 12 patients without nodal disease who had known gross (4 patients) or microscopic (8 patients) residual tumor following attempted curative resection. The pathologic status of the hilar and mediastinal lymph nodes was the most significant factor affecting the frequency of metastatic relapse, with 19% of patients with N0, 33% of those with N1, and 69% of those with N2 disease developing distant disease. The low overall rate of recurrence intrathoracically (16%) confirms that postoperative radiotherapy is effective in preventing local relapse even in patients with proven nodal involvement. The impact of adjuvant radiation therapy on survival cannot be determined from these data, and further data are needed, preferably from well designed prospective studies.

Results of mastectomy and postoperative irradiation in the management of locoregionally advanced carcinoma of the breast.

Between 1955 and 1984, 376 patients with locoregionally advanced breast carcinoma were treated at The University of Texas M. D. Anderson Cancer Center with mastectomy and irradiation and without adjuvant chemotherapy. Patients with inflammatory carcinoma or synchronous bilateral primary tumors were excluded. There were 202 patients with Stage IIIA disease and 174 patients with Stage IIIB disease (AJC Staging--1983). In 124 patients the surgical management was confined to the breast only--total mastectomy (BR) and in 252 dissection of the axilla was performed--extended total, modified radical, or classic radical mastectomy (BR + AX). All patients had postoperative irradiation. The follow-up period ranged between 8 and 34 years. At 10 years, the actuarial disease-specific, relapse-free survival (DSRFS) rate for the entire group was 40%, and the actuarial locoregional control rate was 82%. For patients with Stage IIIA disease the DSRFS was 48% and locoregional control rate was 88%. For those with Stage IIIB disease, the figures were 30% and 74%, respectively. Most of the failures occurred within 5 years of the mastectomy and essentially all occurred within 10 years. When analyzed by type of surgery, both the locoregional control and DSRFS rates were improved by the axillary dissection, the difference being largely caused by fewer axillary node recurrences after dissection of both the breast and axilla than after removal of the breast alone. In the 252 patients in whom the axilla was assessed, the number of positive nodes was a powerful predictor of both locoregional control and survival. The DSRFS rates at 10 years for patients with 0, 1-3, and greater than or equal to 4 positive nodes were 63%, 48%, and 30%, respectively. The actuarial locoregional control rates at 10 years exceeded 95% for patients with 0-3 positive nodes and 75% for those with greater than or equal to 4 nodes. These results show that locoregionally advanced breast cancer is not a uniformly fatal disease when treated without chemotherapy and provide a baseline upon which to assess the value of adjuvant systemic therapy for this stage of disease.