Daniel E. Kenady

Hot flashes in postmenopausal women treated for breast carcinoma: prevalence, severity, correlates, management, and relation to quality of life.

Research on hot flashes (HFs) after the diagnosis and treatment of breast carcinoma (BC) is scarce. To our knowledge, this research represents the second study of HF prevalence and severity in women with BC and the first study of 1) correlates of HF prevalence and severity, 2) use of HF management strategies, and 3) the relation between HFs and quality of life (QOL) among women with BC.

PSYCHOSOCIAL ADJUSTMENT AND QUALITY OF LIFE IN WOMEN WITH BREAST CANCER AND BENIGN BREAST PROBLEMS: A CONTROLLED COMPARISON

Comparison of psychosocial adjustment in women with breast cancer (BC) and women with benign breast problems (BBP) has been hampered by a failure to control for age differences between these groups, as well as a failure to assess positive psychosocial adaptation in addition to psychological distress. Age-matched women with breast cancer (n = 80) and benign breast problems (n = 80) completed measures of psychological distress, positive psychosocial adaptation, and general quality of life (QOL). Breast cancer patients had completed primary treatment for breast cancer a mean of 24.6 months prior to participation (range, 6-57 months). Comparison of the BC and BBP groups indicated that the BC group reported (1) poorer physical health and functioning, (2) no differences in psychological distress, and (3) greater positive psychosocial adaptation, such as improved life outlook, enhanced interpersonal relationships, and deeper spiritual and religious satisfaction. Results support the theoretical position that cancer is a transitional event, that is, a traumatic event that alters an individuals assumptive world with the potential to produce long-lasting changes of both a positive as well as negative nature. This underscores the importance of using measures of both psychological distress and positive psychosocial adaptation when assessing psychological adjustment following transitional events such as breast cancer.

Postmastectomy / Postlumpectomy Pain in Breast Cancer Survivors

Few studies have focused on careful assessment of postmastectomy pain (PMP); a chronic neuropathic pain syndrome that can affect women postlumpectomy or postmastectomy for breast cancer (BC). Study aims were to determine the prevalence of PMP in an outpatient sample of breast cancer survivors (BCS), describe subjective and objective characteristics of PMP, and examine the relationship between PMP and quality of life. Breast cancer survivors (n = 134) participated in telephone interviews, and those reporting PMP (n = 36) were invited to a pain center for further evaluation and treatment. Results show PMP is a distinct, chronic, pain syndrome affecting 27% of BCS. Findings support the need for clinical trials evaluating the effectiveness of nonpharmacological or cognitive behavioral therapies in alleviating mild to moderate PMP.

Preoperative chemoradiation in fixed distal rectal cancer: dose time factors for pathological complete response

PURPOSE Preoperative chemoradiation is being utilized extensively in the treatment of rectal cancer. However, a variety of dose time factors in both delivery of chemotherapy and irradiation remain to be established. This study was undertaken to examine the impact of dose time factors on pathological complete response (pCR) rates following preoperative chemoradiation for fixed rectal cancer. METHODS AND MATERIALS Thirty-three patients with fixed rectal cancers were treated with combined 5-fluorouracil (5-FU) chemotherapy and pelvic radiation. Twenty-one patients received bolus 5-FU during the first 3-5 days of radiation and repeated on days 28-33 of their radiation treatment. Twelve patients were treated with continuous infusion (CI) 5-FU, 225 mg/m(2) for the duration of the pelvic radiation. Fifteen patients received a planned total radiation dose of 45 to 50 Gy and 18 patients received a dose of 55 to 60 Gy. Surgical resection was then carried out 6-8 weeks after completion of treatment. RESULTS Diarrhea was the most frequent acute toxicity. Grade 3 diarrhea was observed in 6 patients requiring treatment interruption and was not related to the chemotherapy regimen. There was no Grade 4 or 5 toxicity. pCR was observed in 2 of 21 (10%) patients treated with bolus 5-FU as compared to 8 of 12 (67%) for patients treated with CI (p = 0.002). pCR were observed in 8 of 18 (44%) patients receiving radiation dose > or = 5500 cGy as compared to 2 of 15 (13%) patients treated to a dose < or = 5000 cGy (p = 0.05). In the high-dose radiation (> or = 5500 cGy) group, a significant difference in pCR rate was observed in patients treated with CI, 8 of 12 (67%) (p = 0.017) as compared with bolus 5-FU (0 of 6). There was no significant difference in operative morbidity or in wound healing between patients treated with bolus 5-FU or CI or within the groups treated with low or high doses of radiation. Three patients have developed local recurrence at 14 and 24 months, two in the low-dose group treated with bolus 5-FU and one patient in the CVI group. The overall 5-year survival for the whole group is 71%. CONCLUSION Dose intensity of 5-FU and dose of radiation correlate significantly with the likelihood of achieving a pCR. Continuous infusion 5-FU (CI) and a preoperative radiation dose of 5500 cGy or higher can achieve pCR rates of approximately 50%, even in fixed cancers of the rectum.

Stability and change in posttraumatic stress disorder symptoms following breast cancer treatment: a 1-year follow-up.

While some recent research has examined the prevalence and severity of posttraumatic stress disorder (PTSD)‐like symptoms following cancer treatment, no research has examined temporal change or stability in these symptoms in cancer survivors. Female breast cancer survivors (n=46) participated in an initial telephone interview and a follow‐up interview 12 months later. PTSD symptoms associated with breast cancer were assessed using the PTSD Checklist—Civilian version (PCLC). In general, PTSD symptoms in this population did not diminish over time. While group analyses indicated that PCLC‐total and subscale scores were stable across the two assessments, analyses of PCLC scores indicated that many patients exhibited fairly large (>0.5 S.D.) increases and/or decreases in PCLC‐total or subscale scores. Some evidence suggested that decreases in PCLC scores between the two study assessments were associated with greater social support and experience of fewer traumatic stressors prior to breast cancer diagnosis. Most significantly, the research suggested that women with greater PTSD symptoms at the initial interview were less likely to participate in the follow‐up interview. Implications of this for research and clinical management of PTSD in this population are discussed. Copyright

Combined chemotherapy, radiation, and surgery for epithelial cancer of the anal canal

Combined chemotherapy and radiation therapy have been reported to produce a high incidence of complete regression of epithelial cancer of the anal canal, resulting in prolonged disease‐free survival. This modality has been advocated as an alternative to abdominoperineal resection as a primary treatment for this disease. Our group treated 19 patients between 1979 and 1985. Treatment included two infusions of 5‐fluorouracil (1000 mg/m2/24 hours), one dose of mitomycin C (15 mg/m2), and simultaneous whole‐pelvis radiation (3000 rad). The complete response rate was 88%. Three patients had anal cancer incompletely controlled by that therapy. They underwent abdominoperineal resections and are alive without disease at 10, 39, and 43 months, respectively. Actuarial disease‐free survival at 40 months was 87.5 ± 8.8 (% ± standard error of the mean [SEM]). Complications included gastrointestinal, hematologic, and cutaneous toxicity. These results confirmed a high complete response rate to this therapy. Local treatment failures may occur, but these may be salvaged with abdominoperineal resection.

A multicenter phase II study of tgDCC-E1A for the intratumoral treatment of patients with recurrent head and neck squamous cell carcinoma.

The anti‐cancer gene, E1A, can be complexed to a lipid carrier, DC‐Cholesterol:DOPE, to form tgDCC‐E1A, which can be injected directly into tumors.

Thymosin immunotherapy in patients with small cell carcinoma of the lung: correlation of in vitro studies with clinical course.

Previous studies suggest that the mechanism of action of thymosin is reconstitution of immune defects rather than augmentation of relatively normal levels of cellular immunity. To test this hypothesis, we correlated in vitro assays with clinical course in 55 patients with bronchogenic carcinoma who were randomized to receive subcutaneous inoculations of thymosin 60 mg/m2 (T60), thymosin 20 mg/m2 (T20), or no thymosin (P) twice weekly during the first six weeks of an intensive chemotherapy program. Overall tumor response did not differ significantly among the three treatment groups (p >.12); however, survival of the T60 group was significantly greater than that of the P group (p =.017). Duration of response for patients achieving a complete remission was significantly longer in the T60 group than in the P group (p =.02). In an attempt to define an association between the increased survival of the T60 group and in vitro assays that show changes with tumor presence and extent, comparisons were made between survival and pretreatment peripheral blood levels of carcinoembryonic antigen (CEA), α2HS‐glycoprotein (α2HS), and total thymus‐dependent lymphocytes (T cells). Independent of therapy, pretreatment CEA levels correlated directly with tumor extent (p=.004) and inversely with degree of tumor response (p=.006) and survival (p=.006). The effect of T60 compared with the P group on survival was similar in patients with pretreatment CEA levels >4 Ng/ml and those with levels >4 Ng/ml. However, among those with pretreatment total T‐cell and α2HS levels below the median for all patients, survival of the T60 group was significantly greater than that of the P group (p=.006 and p=.036, respectively); for patients with higher pretreatment total T‐cell and α2HS levels, survival did not differ significantly between the T60 and P groups (p=.28 and p=.17, respectively). Analysis by tests of interaction shows that the effect of T60 on survival depended on pretreatment levels of α2HS (p=.046) and, to some extent, total T‐cells (p=.17). Thus the association between survival and type of treatment may be related to pretreatment levels of these two parameters of cellular immunity. These results support the hypothesis that patients with relatively low levels of immunity benefit most from administration of thymosin. Additional studies with larger patient populations and other tumors are needed to confirm these findings. Cancer 43:863–870, 1979.

PHYSICAL SYMPTOMS, DISTRESS, AND BREAST CANCER RISK PERCEPTIONS IN WOMEN WITH BENIGN BREAST PROBLEMS

Physical symptoms, general and breast cancer-specific distress, and perceived breast cancer risk were assessed in 66 women with benign breast problems (BBP) and 66 age-matched healthy comparison (HC) women. BBP women reported significantly greater worry about breast cancer than HC women. Breast symptom incidence and breast cancer risk perceptions were found to mediate group differences in breast cancer worry. Hierarchical regression analyses indicated that perceptions of control over a potential breast cancer prognosis moderate the impact of breast symptoms on reports of breast cancer worry. Implications for risk counseling with BBP women are discussed.

High-Dose Intra-Arterial Cisplatin Boost With Hyperfractionated Radiation Therapy for Advanced Squamous Cell Carcinoma of the Head and Neck

PURPOSE To evaluate the tolerance and efficacy of intra-arterial (IA) cisplatin boost with hyperfractionated radiation therapy (HFX-RT) in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS Forty-two patients with locally advanced primary SCCHN were treated on consecutive phase I/II studies of HFX-RT (receiving a total of 76.8 to 81.6 Gy, given at 1.2 Gy bid) and IA cisplatin (150 mg/m(2) received at the start of and during RT boost treatment). RESULTS Acute grade 3 to 4 toxicities were as follows: grade 4 and grade 3 mucosal toxicity occurred in three (7%) and 31 patients (69%), respectively, and grade 3 hematologic, infectious, and skin events occurred in one patient each. Eight of 24 patients (33%) were unable to receive a second planned dose of IA cisplatin because of general anxiety (n = 5), nausea and/or emesis (n = 2), or asymptomatic occlusion of an external carotid artery (n = 1). Thirty-seven patients (88%) experienced complete response (CR) at primary site. Twenty-nine (85%) of 34 patients presenting with nodal disease experienced CR. The actuarial 2-year rates of locoregional control and disease-specific and overall survival are 73%, 63%, and 57%, respectively, with a median active follow-up of 30 months. CONCLUSION In this highly unfavorable subset of patients, these results seem superior to previously reported chemoradiation regimens in more favorable patients. Use of a second dose of IA cisplatin boost was associated with increased toxicity without obvious therapeutic gain. This novel strategy allows for an incremental increase in the treatment intensity of the HFX-RT regimen recently established as superior to once-a-day RT.