Paul J. Chuba

Bilateral Risk for Subsequent Breast Cancer After Lobular Carcinoma-In-Situ: Analysis of Surveillance, Epidemiology, and End Results Data

PURPOSE Noninvasive lesions involving the lobules of the breast are increasingly diagnosed as incidental microscopic findings at the time of lumpectomy or core-needle biopsy. We investigated the incidence rates of invasive breast cancer (IBC) after a diagnosis of lobular carcinoma-in-situ (LCIS) by using Surveillance, Epidemiology, and End Results (SEER) data. PATIENTS AND METHODS Patients (N = 4,853) having a diagnosis of primary LCIS in the time period of 1973 to 1998 were identified using the SEER Public Use CD-ROM data. The database was then searched for patients with subsequent primary IBC occurrences (n = 350). The clinical and pathologic characteristics of patients with subsequent primary IBCs were compared with the characteristics of patients with primary IBCs attained during the same time period (N = 255,114). RESULTS The incidence of IBC increased over time from diagnosis of LCIS, with 7.1% +/- 0.5% incidence of IBC at 10 years. IBCs detected after partial mastectomy occurred in either breast (46% ipsilateral and 54% contralateral); however, after mastectomy, most IBCs were contralateral (94.7%). IBCs occurring after LCIS more often represented invasive lobular histology (23.1%) compared with primary IBCs (6.5%). The standardized incidence ratio (the ratio of observed to expected cases) for developing IBC was 2.4 (95% CI, 2.1 to 2.6) adjusted for age and year of diagnosis. CONCLUSION LCIS is associated with increased risk of subsequent invasive disease, with equal predisposition in either breast. The minimum risk of developing IBC after LCIS is 7.1% at 10 years.

Sarcoma as a second malignancy after treatment for breast cancer

BACKGROUND Second malignant neoplasms may be a consequence of radiotherapy for the treatment of breast cancer. Prior studies evaluating sarcomas as second malignant neoplasms in breast cancer patients have been limited by the numbers of patients and relatively low incidence of sarcoma. Using data from the Surveillance, Epidemiology and End Results registries, we evaluated the influence of radiation therapy on the development of subsequent sarcomas in cases with primary breast cancer. METHODS Cases with primary invasive breast cancer (n = 274,572) were identified in the Surveillance, Epidemiology and End Results Cancer Incidence Public-Use Database (1973-1997). The database was then queried to determine the cases developing subsequent sarcomas (n = 263). Eighty-seven of these cases received radiation therapy, and 176 had no radiation therapy. The cumulative incidence of developing secondary sarcoma and the survival post developing secondary sarcoma were determined by the Kaplan-Meier method. RESULTS The occurrence of sarcoma was low, regardless of whether cases received or did not receive radiation therapy: 3.2 per 1,000 (SE [standard error] = 0.4) and 2.3 per 1,000 (SE = 0.2) cumulative incidence at 15 years post diagnosis, respectively (p = 0.001). Of the sarcomas occurring within the field of radiation, angiosarcoma accounted for 56.8%, compared to only 5.7% of angiosarcomas occurring in cases not receiving radiotherapy. The cumulative incidence of angiosarcoma at 15 years post diagnosis was 0.9 per 1,000 for cases receiving radiation (SE = 0.2) and 0.1 per 1,000 for cases not receiving radiation (SE < 0.1). Overall survival was poor for cases of sarcoma after breast cancer (27-35% at 5 years), but not significantly different between patients receiving or not receiving radiation therapy for their primary breast cancer. CONCLUSIONS Radiotherapy in the treatment of breast cancer is associated with an increased risk of subsequent sarcoma, but the magnitude of this risk is small. Angiosarcoma is significantly more prevalent in cases treated with radiotherapy, occurring especially in or adjacent to the radiation field. The small difference in risk of subsequent sarcoma for breast cancer patients receiving radiotherapy does not supersede the benefit of radiotherapy.

Hyperbaric oxygen therapy for radiation-induced brain injury in children

Radiation‐induced necrosis (RIN) of the brain is a complication associated with the use of aggressive focal treatments such as radioactive implants and stereotactic radiosurgery. In an attempt to treat patients with central nervous system (CNS) RIN, ten patients received hyperbaric oxygen treatment (HBOT).

CUTANEOUS MELANOMA IN CHILDHOOD AND ADOLESCENCE

Using population-based data from the Surveillance Epidemiology and End Results Program of the National Cancer Institute, melanoma occurring during childhood was evaluated. Compared to adult cases of melanoma, childhood cases had a higher proportion of females (61%) and non-Caucasians (6.5%). The incidence of melanoma increased 85% among 15- to 19-year-olds from 1973 to 1996. Incidence for 15- to 19-year-olds was higher in southern (23.9/million) than northern registries (14.5/million). Non-Caucasians had 3-30% of the cases expected compared to Caucasians. Overall survival of children/adolescents with melanoma was 89% and 79% at 5 and 20 years post diagnosis, respectively. The majority of deaths were directly attributed to melanoma (72%).

Cloning and DNA sequence of plasmid determinant iss, coding for increased serum survival and surface exclusion, which has homology with lambda DNA

SummaryEscherichia coli K12 cells carrying a cloned 1.4 kb HindIII fragment from plasmid ColV2-K94, showed increased survival in guinea pig serum. The recombinant plasmid also conferred group II surface exclusion, i.e. the cells were reduced in recipient ability towards the incoming plasmid R538drd in conjugation experiments. Southern blotting suggested homology with bacteriophage lambda DNA and to the insertion element IS2. Determination of the DNA sequence of the fragment demonstrated the presence of a truncated IS2 (165 bp), separated by 250 bp from a 900 bp stretch of homology with lambda DNA, beginning within the Rz gene and continuing in the rightward direction on the lambda map. A 97 amino acid open reading frame (ORF) adjacent to Rz and on the opposite strand, remained intact in iss, with several amino acid changes. The ORF in iss is preceded by sequences resembling prokaryotic ribosome binding sites and promoters.

CONFORMAL MIXED NEUTRON AND PHOTON IRRADIATION IN LOCALIZED AND LOCALLY ADVANCED PROSTATE CANCER: PRELIMINARY ESTIMATES OF THE THERAPEUTIC RATIO

PURPOSE To determine the incidence of chronic toxicity and the probability of biochemical and histologic complete response among patients with nonmetastatic prostate cancer, treated with three dimensional (3D) conformal mixed neutron and photon irradiation. METHODS AND MATERIALS Between November 1991 and December 1994, 151 patients with prostate cancer were entered in three prospective dose-finding studies of conformal mixed neutron and photon irradiation. Patients with low stage, low to intermediate grade prostate cancer (T1-2NXM0, Gleason Score < or = 7) received 38 Photon Gy (PhGy) plus 9 (51 patients) or 10 (53 patients) Neutron Gy (NGy) to the prostate and seminal vesicles. Forty-seven patients with locally advanced prostate cancer (T3-4 N0-1 M0 and/or Gleason Score > or = 8) received 15 NGy + 18 PhGy to the prostate and seminal vesicles and 9 NGy + 18 PhGy to the pelvic lymph nodes. RESULTS The median follow-up was 16 months (range: 3-30 months). There was no Grade 3-5 GI or GU toxicity recorded. At 20 months, the actuarial rates of Grade 2 GI morbidity were 6 and 29% for the 9-10 and 15 NGy protocols, respectively (p = 0.07). At 20 months, the incidences of Grade 2 GU morbidity were 4 and 16%, respectively (p = 0.08). Stiffness in flexing or abducting the hips was seen in 20 and 42% of patients receiving 9-10 and 15 NGy, respectively (p = 0.01). Potency was maintained in 65% of all patients. Among patients with an initial PSA < or = 10, 100% had a 12-month PSA < 2 and 78% < 1 ng/ml. Negative postradiation biopsies were seen in 30% of patients 6 months, 79% at 12 months, and 84% of patients at 18 months. CONCLUSION The use of conformal mixed neutron and photon irradiation has been well tolerated with no severe bladder or rectal complications observed. However, because of the enhanced toxicity seen with 15 NGy, the current maximum dose levels of neutron irradiation have been limited to 11 NGy.

Second solid malignancies among children, adolescents, and young adults diagnosed with malignant bone tumors after 1976: follow-up of a Children's Oncology Group cohort.

The growing number of individuals surviving childhood cancer has increased the awareness of adverse long‐term sequelae. One of the most worrisome complications after cancer therapy is the development of second malignant neoplasms (SMNs).

A Pilot Study of Low-Dose Anti-Angiogenic Chemotherapy in Combination With Standard Multiagent Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma Family of Tumors: A Children's Oncology Group (COG) Phase II Study NCT00061893

The aims of this study were to determine the feasibility of the combination of low dose, anti‐angiogenic chemotherapy with standard therapy for patients with metastatic Ewing sarcoma (ES), and to obtain preliminary outcome data.

Neoadjuvant estramustine and etoposide followed by concurrent estramustine and definitive radiotherapy for locally advanced prostate cancer: feasibility and preliminary results.

PURPOSE Current therapy for locally advanced prostate cancer is suboptimal. A treatment regimen was designed to improve systemic control by neoadjuvant targeting of hormone-sensitive and -insensitive micrometastatic disease and to improve local control by escalating the biologic effective dose to the prostate using estramustine (EMP) concurrently with radiotherapy. PATIENTS AND METHODS Eighteen patients with locally advanced prostate cancer (Stages T3/T4 or T1c/T2b/T2c with a Gleason score of > or =7 and a serum PSA >15 ng/ml) were entered onto this trial. Therapy consisted of two 21-day cycles of oral estramustine (10 mg/kg/day) in three divided doses and oral etoposide (50 mg/m(2)/day, in two divided doses), followed by concurrent estramustine (10 mg/kg/day, PO) and three-dimensional conformal radiotherapy. RESULTS Two patients required discontinuation of chemotherapy due to development of Grade 3 and 4 toxicity. All others completed both components of therapy per protocol guidelines. Minor toxicities included alopecia (100% of patients), anemia (69%), leukopenia (37%), thrombocytopenia (19%), and nausea (6%) but did not require dose modifications. There were no fatalities. Actuarial 3-year overall survival and disease-free survival (DFS) were 88% and 73%, respectively. Local control rate, assessed by repeated prostate biopsies at 18 months post completion of therapy, was 71%. CONCLUSION The described regimen is well tolerated, and preliminary efficacy data are encouraging. The underlying concepts of early targeting of both hormone-sensitive and -insensitive micrometastatic clones, in combination with aggressive local therapy, warrant further investigation.

Radiation therapy for endometrial cancer in patients treated for postoperative recurrence

PURPOSE To retrospectively evaluate the outcome and risk factors in patients treated with radiation for endometrial cancer at time of recurrence. MATERIALS AND METHODS Three hundred ninety-nine women were treated with radiation therapy for endometrial cancer at KCI/WSU from January 1980 to December 1994. Of these, 26 patients treated primarily with surgery received radiation therapy at the time of recurrence. Median time to recurrence after surgery was 8 months, with all recurrences occurring within 24 months. Twenty-four patients had recurrences in the vaginal cuff, vagina, or pelvis. These patients received external-beam radiation to the pelvis (45.00-50.40 Gy) and periaortic lymph nodes (45.00-50.00 Gy), along with a boost given by external-beam radiation or brachytherapy (16.00-30.00 Gy). Mean follow-up was 15 months (range 1-85 months). RESULTS The 2-year survival was 50% and median survival was 16 months (survival range 1-85 months). Of 26 patients, 54% (14) failed locally following radiation therapy. Factors indicative of poor survival included histology (sarcoma, poorly differentiated adenocarcinoma), grade, and lymph node positivity. Histological differentiation influenced local control; lymphovascular space invasion was of borderline significance with regard to local control. CONCLUSION Local control and survival for surgically treated endometrial cancer patients who receive radiation at the time of recurrence are poor, with the exception of those patients with recurrent disease limited to the vagina. Early detection of recurrence may improve outcome. Pathologic risk factors may identify those patients at risk for extrapelvic recurrence. Alternative treatment modalities need to be developed for this high-risk group of patients.