William D. Bloomer

Primary radiation therapy for early breast cancer: The experience at the joint center for radiation therapy

Abstract The results of primary radiation therapy in 176 consecutive patients with clinical Stage I and II carcinoma of the breast were reviewed. Median follow-up time was 47 months. The overall breast relapse rate was 7%. Patients undergoing interstitial implantation had a significantly lower breast relapse rate (1%) than patients not undergoing implantation (11 %). Breast relapse was more common in patients undergoing incisional or needle biopsy (17 %), compared to patients treated after excisional biopsy (5 %). In patients undergoing excisional biopsy, but not interstitial implantation, breast relapse was related to external beam dose. Twelve percent of the patients who received less than 1600 ret dose relapsed in the breast, compared to none of the 19 patients who received more than 1700 ret dose. These results imply that supplemental irradiation to the primary tumor area is required following excisional biopsy of a primary breast cancer when 4500–5000 rad is delivered to the entire breast.

Stage III adenocarcinoma of the endometrium: two prognostic groups.

Abstract Between July 1968 and December 1976, 26 patients with surgical-pathologic Stage III adenocarcinoma of the endometrium were treated at the Joint Center for Radiation Therapy. In 15 patients, extrauterine disease was confined to the ovary and/or fallopian tube (Group A). In 11 patients, disease extended beyond these organs to the vagina or other pelvic structures (Group B). Treatment included a combination of radiation therapy and surgery in all but one patient, who was treated by radiation therapy alone. The median follow-up was 65 months and the median time to relapse 9 months. The actuarial relapse-free 5-year survival for all Stage III patients was 54%; it was significantly different ( P = 0.01) for Group A (80%) and Group B (15%). The nature of extrauterine involvement in surgical-pathologic Stage III adenocarcinoma of the endometrium is of major prognostic significance.

The complication probability factor: a method for selection of radiation treatment plans

The problem of selecting the best radiation treatment plan from several that may offer subtle differences has been considered. A method is introduced in which the concept of a complication probability factor (CPF) can be used to quantify the relative merits of such treatment plans. The CPF is a variant of integral dose and consists of a weighted volume of irradiated normal tissue which may relate to radiation-related complications. Treatment plans for irradiation of a pelvic tumour volume using parallel opposed, 360 deg rotational and four-field techniques with X-ray beams of 4, 8, 22, and 45 MV have been analyzed to demonstrate the utility of the method. This analysis suggests that complex radiation delivery techniques may offer a substantial improvement in dose distribution characteristics, while higher beam energies are relatively less advantageous.

Stage II endometrial carcinoma: 10-year follow-up of combined radiation and surgical treatment

Abstract Fifty-five patients with histologically confirmed stage II adenocarcinoma of the corpus uteri were treated with combined radiation therapy and surgery and followed for 2 to 10 years. The overall survival at 5 and 10 years is 75 and 56%, respectively; the age-adjusted survival is 93 and 73%, respectively. Disease-free survival is 88% at 2 years and 83% at both 5 and 10 years. Although 10 patients (18%) failed treatment, each local pelvic recurrence was accompanied by dissemination elsewhere. Histological grade and extent of involvement of the uterine cervix at time of examination under anesthesia are statistically significant prognostic factors. Age, depth of uterine sounding, and depth of myometrial invasion by tumor were not of prognostic value. We conclude that combined preoperative external beam and intracavity radiation with total abdominal hysterectomy and bilateral salpingo-oophorectomy is the preferred treatment for stage II endometrial carcinoma ecause of the excellent survival and low morbidity. Furthermore, both histologic grade and extent of cervical involvement predict the natural history of stage II disease.

Parasternal lymphoscintigraphy: Implications for the treatment planning of internal mammary lymph nodes in breast cancer☆

Abstract Parasternal lymphoscintigraphy is an easily performed technique for visualizing and accurately determining thethree dimensional location of internal mammary lymph nodes. Sixty-eight women with primary or locally recurrent breast cancer underwent parasternal lymphoscintigraphy before treatment planning. The mean depth and lateral position of the internal mammary nodes were 1.8. ± 0.9 cm and 2.4 ± 0.9 cm respectively. Thirteen per cent of the nodes would have been undertreated by the standard tangential technique used at our institution. Six of 15 patients whose treatment plans were examined retrospectively had at least 1 lymph node undertreated by the standard tangential tec hnique. Thus, although standard tangential portals provide adequate coverage for the internal mammary lymph nodes in a majority of patients, parasternal lymphoscintigraphy can insure complete coverage of this lymph node group.

The role of subcellular localization in assessing the cytotoxicity of iodine-125 labeled iododeoxyuridine, iodotamoxifen, and iodoantipyrine

There is abundant evidence that Auger effects from125I are singularly damaging if localized within DNA as the thymidine analogue125I-iododeoxyuridine (125IUdR). Recent work with125I-labeled intercalating agents and steroid sex hormones extends these observations by showing cytotoxicity with125I in sites other than the DNA backbone. We have compared the cytotoxicity of125IUdR,125I-iodotamoxifen, a non-steroidal antiestrogen that is translocated from the cytoplasm to the nucleus of receptor containing cells, and125I-iodoantipyrine, a biological indicator of the body water space, in human breast cancer cells (MCF-7) and report that cytotoxicity is critically dependent upon subcellular localization. When clonogenic survival of MCF-7 cells is expressed as a function of the concentration of125IUdR,125ITAM and125IAP in the culture media, the D37 values are 8·10−4, 2.3 and 68 μCi/ml, respectively. However, when survival is expressed as a function of the nucleic acid and protein subcellular fraction,125ITAM is just about as toxic as125IUdR localized within the DNA backbone.

Combined chemotherapy and radiation therapy for advanced carcinoma of the cervix

Ten patients with advanced squamous cell carcinoma of the uterine cervix received induction chemotherapy with cis-platinum, mitomycin-C, vincristine, and bleomycin (BOMP) over a 5 week period, followed by radiotherapy with concomitant weekly cisplatinum. Two patients were FIGO stage I-B barrel-shaped, five were stage II-B, and three were III-B. All patients responded to induction chemotherapy with five complete and five partial responses. At the completion of radiation therapy, nine patients had negative biopsies. One patient never reached a complete response and died of distant metastasis. Another underwent total exenteration for a central recurrence and was found to have microscopic paraaortic lymph node involvement. A third recurred in the parametrium. Two patients with barrel-shaped tumors underwent extrafascial hysterectomies; both had negative specimens and tolerated surgery well. Although follow-up is short, this new approach for advanced carcinoma of the cervix yielded excellent results and was well tolerated.

Iodine-125 cytotoxicity: implications for therapy and estimation of radiation risk.

Abstract The consequences of differential subcellular radionuclide accumulation, particularly within nuclear structures, have important implications for the design and development of radiopharmaceuticals for therapy as well as for the estimation of radiation risks. There is a growing body of experimental data demonstrating that localization of 125 I within nuclear structures results in marked cytotoxicity. This report reviews the physical and biological consequences of 125 I decay when 125 I is incorporated into cells as iododeoxyuridine or iodotamoxifen.

Therapeutic implications of iodine-125 cytotoxicity.

Abstract The biological consequences of differential subcellular radionuclide accumulation within nuclear structures have important implications for the design and development of new therapeutic agents for cancer management. A growing body of experimental data demonstrates that localization of 125 I within the genome results in marked cytotoxicity. Investigations of iodine-125 labeled iododeoxyuridine, DNA intercalators and tamoxifen are reviewed as representative of this new group of potential radiotherapeutic agents.

Nitrotriazole- and Imidazole-Based Amides and Sulfonamides as Antitubercular Agents

ABSTRACT Twenty-three 3-nitrotriazole-based and 2-nitroimidazole-based amides and sulfonamides were screened for antitubercular (anti-TB) activity in aerobic Mycobacterium tuberculosis H37Rv by using the BacTiter-Glo (BTG) microbial cell viability assay. In general, 3-nitrotriazole-based sulfonamides demonstrated anti-TB activity, whereas 3-nitrotriazole-based amides and 2-nitroimidazole-based amides and sulfonamides were inactive. Three 3-nitrotriazole-based sulfonamides (compounds 4, 2, and 7) demonstrated 50% inhibitory concentration (IC50), IC90, and MIC values of 0.38, 0.43, and 1.56 μM (compound 4), 0.57, 0.98, and 3.13 μM (compound 2), and 0.79, 0.87, and 3.13 μM (compound 7), respectively. For 3-nitrotriazole-based sulfonamides, anti-TB activity increased with lipophilicity, whereas the one-electron reduction potential (E1/2) did not play a role. 2-Nitroimidazole-based analogs, which were inactive in the BTG assay, were significantly more active in the low-oxygen assay and more active than the 3-nitrotriazoles. All active nitrotriazoles in the BTG assay were similarly active or more potent (lower MIC values) against resistant strains, with the exception of compounds 2, 3, 4, and 8, which demonstrated greater MIC values against isoniazid-resistant strains. Five 3-nitrotriazole-based sulfonamides demonstrated activity in infected murine J774 macrophages, causing log reductions similar to those seen with rifampin. However, some compounds caused toxicity in uninfected macrophages. In conclusion, the classes of 3-nitrotriazole-based amides and sulfonamides merit further investigation as potential antitubercular agents.