Emotional Problems Prior to Adjuvant Radiation Therapy for Breast Cancer.

BACKGROUND/AIM: Being scheduled for radiotherapy can cause emotional distress. This study aimed to identify risk factors in 338 patients assigned to radiotherapy for breast cancer. PATIENTS AND METHODS: Nineteen potential risk factors including the COVID-19 pandemic were investigated for associations with the six emotional problems included in the National Comprehensive Cancer Network Distress Thermometer. RESULTS: Worry and fears were significantly associated with age ≤60 years; sadness with age and Karnofsky performance score (KPS) <90; depression with KPS and Charlson Comorbidity Index ≥3; loss of interest with KPS. Trends were found for associations between sadness and additional breast cancer/DCIS, Charlson Index and chemotherapy; between depression and additional breast cancer/DCIS, treatment volume and nodal stage N1-3; between nervousness and additional breast cancer/DCIS, mastectomy and triple-negativity; between loss of interest and Charlson Index, family history of breast cancer/DCIS, invasive cancer, chemotherapy, and treatment volume. The COVID-19 pandemic did not increase emotional problems. CONCLUSION: Several risk factors for emotional problems were identified. Patients with such factors should receive psychological support well before radiotherapy.

Results of Tri-Modality Therapy for Rectal Cancer in Elderly Patients.

BACKGROUND/AIM: Elderly cancer patients are more prevalent and require special attention. This study focused on the outcome of elderly (≥65 years) rectal cancer patients treated with tri-modality therapy. PATIENTS AND METHODS: A total of 105 patients receiving neoadjuvant radio-chemotherapy and resection for locally advanced rectal cancers were retrospectively evaluated. Nine characteristics were analyzed for loco-regional control (LRC), metastases-free survival (MFS) and overall survival (OS) including tumor location, gender, age, performance status, radiotherapy technique, primary tumor/lymph node categories, downstaging and histological grading. RESULTS: The 5-year rates of LRC, MFS and OS were 91%, 78% and 87%, respectively. Radio-chemotherapy was not completed in 12 patients (11%) due to toxicity; 18 patients (17%) experienced grade 3 toxicities. A total of 29 patients (28%) had surgical complications. On multivariate analyses, MFS was significantly associated with downstaging (p=0.003) and OS with lower histological grade (p=0.013). CONCLUSION: Tri-modality therapy resulted in promising outcomes and was tolerated reasonably well by elderly patients. Prognostic factors were identified that may help personalize future treatment.

Statins and Metformin Use Is Associated with Lower PSA Levels in Prostate Cancer Patients Presenting for Radiation Therapy.

BACKGROUND: A possible association between the level of prostate specific antigen (PSA) and the use of some commonly prescribed medications has been reported in recent studies. Most of these studies were carried out in general populations of men who were screened for prostate cancer using the PSA test. We reported on the association between the initial PSA level and the use of statins, metformin and alpha-blockers in patients who were diagnosed with prostate cancer and presented for radiation therapy. METHODS: Three hundred and eighty one patients treated between the years of 2000-2005 and 2009-2012 were included in this retrospective study. The information about statin, metformin and alpha-blockers use was recorded immediately prior to treatment. Differences in PSA levels prior to treatment by medication status were estimated using univa-riate and multivariate linear regression on log PSA values. RESULTS: Compared with men who were not on these medications, the PSA level at presentation was 20% lower for statin users (p = 0.002) and 33% lower for metformin users (p = 0.004). We did not observe statistically significant associations between the use of statins or metformin and cancer stage, National Comprehensive Cancer Network (NCCN) risk score, or therapy outcome. A statistically significant association between the NCCN risk score and the use of alpha-blockers was observed (p = 0.002). CONCLUSIONS: We found that statins and metformin were associated with lower PSA levels in prostate cancer patients to an extent that could influence management decisions. We found no statistically significant associations between the use of these medications and treatment outcomes.

Outcome and toxicity for patients treated with intensity modulated radiation therapy for localized prostate cancer.

PURPOSE: We evaluate long-term disease control and chronic toxicities observed in patients treated with intensity modulated radiation therapy for clinically localized prostate cancer. MATERIALS AND METHODS: A total of 302 patients with localized prostate cancer treated with image guided intensity modulated radiation therapy between July 2000 and May 2005 were retrospectively analyzed. Risk groups (low, intermediate and high) were designated based on National Comprehensive Cancer Network guidelines. Biochemical control was based on the American Society for Therapeutic Radiology and Oncology (Phoenix) consensus definition. Chronic toxicity was measured at peak symptoms and at last visit. Toxicity was scored based on Common Terminology Criteria for Adverse Events v4. RESULTS: The median radiation dose delivered was 75.6 Gy (range 70.2 to 77.4) and 35.4% of patients received androgen deprivation therapy. Patients were followed until death or from 6 to 138 months (median 91) for those alive at last evaluation. Local and distant recurrence rates were 5% and 8.6%, respectively. At 9 years biochemical control rates were 77.4% for low risk, 69.6% for intermediate risk and 53.3% for high risk cases (log rank p = 0.05). On multivariate analysis T stage and prostate specific antigen group were prognostic for biochemical control. At last followup only 0% and 0.7% of patients had persistent grade 3 or greater gastrointestinal and genitourinary toxicity, respectively. High risk group was associated with higher distant metastasis rate (p = 0.02) and death from prostate cancer (p = 0.0012). CONCLUSIONS: This study represents one of the longest experiences with intensity modulated radiation therapy for prostate cancer. With a median followup of 91 months, intensity modulated radiation therapy resulted in durable biochemical control rates with low chronic toxicity.

A front-line window of opportunity phase 2 study of sorafenib in patients with advanced nonsmall cell lung cancer: North Central Cancer Treatment Group Study N0326.

BACKGROUND: The current study was conducted to assess the efficacy and toxicity of sorafenib as front-line therapy in patients with stage IIIB (pleural effusion) or IV nonsmall cell lung cancer (NSCLC). METHODS: Patients received sorafenib 400 mg twice daily by mouth continuously, and were evaluated every 2 weeks during the first 8 weeks. Patients who manifested clinical progression during this period proceeded to receive standard of care. The primary endpoint was confirmed objective tumor response. A 2-stage Fleming design was used such that if at most 1 confirmed partial response (PR) or complete response was observed in the first 20 patients (stage 1), the treatment would be considered ineffective, and further enrollment would be discontinued. RESULTS: Only 1 PR was observed in the first 20 patients. By the time of study closure, 5 additional patients who were already being screened for study inclusion were enrolled. Of the 25 patients (15 women, 10 men; 4 stage IIIB, 21 stage IV; median age, 67 years [range, 45-85 years]), there were 3 (12%) PRs and 6 (24%) cases with stable disease observed. The median time-to-progression and progression-free survival was 2.8 months. Seven (28%) patients remained progression-free at 24 weeks. No grade 3 or higher hematologic adverse events were observed. Thirteen (52%) patients had a grade 3 nonhematologic adverse event, with fatigue (20%), diarrhea (8%), and dyspnea (8%) being the most common. CONCLUSIONS: Sorafenib is not effective as front-line therapy in the general unselected NSCLC population. The window of opportunity design is feasible for estimating the activity of novel compounds.

Radiochemotherapy including cisplatin alone versus cisplatin + 5-fluorouracil for locally advanced unresectable stage IV squamous cell carcinoma of the head and neck.

BACKGROUND AND PURPOSE: The optimal radiochemotherapy regimen for advanced head-and-neck cancer is still debated. This nonrandomized study compares two cisplatin-based radiochemotherapy regimens in 128 patients with locally advanced unresectable stage IV squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Concurrent chemotherapy consisted of either two courses cisplatin (20 mg/m(2)/d1-5 + 29-33; n = 54) or two courses cisplatin (20 mg/m(2)/d1-5 + 29-33) + 5-fluorouracil (5-FU; 600 mg/m(2)/d1-5 + 29-33; n = 74). RESULTS: At least one grade 3 toxicity occurred in 25 of 54 patients (46%) receiving cisplatin alone and in 52 of 74 patients (70%) receiving cisplatin + 5-FU. The latter regimen was particularly associated with increased rates of mucositis (p = 0.027) and acute skin toxicity (p = 0.001). Seven of 54 (13%) and 20 of 74 patients (27%) received only one chemotherapy course due to treatment-related acute toxicity. Late toxicity in terms of xerostomia, neck fibrosis, skin toxicity, and lymphedema was not significantly different. The 2-year locoregional control rates were 67% after cisplatin alone and 52% after cisplatin + 5-FU (p = 0.35). The metastases-free survival rates were 79% and 69%, respectively (p = 0.65), and the overall survival rates 70% and 51%, respectively (p = 0.10). On multivariate analysis, outcome was significantly associated with performance status, T-category, N-category, hemoglobin level prior to radiotherapy, and radiotherapy break > 1 week. CONCLUSION: Two courses of fractionated cisplatin (20 mg/m(2)/day) alone appear preferable, as this regimen resulted in similar outcome and late toxicity as two courses of cisplatin + 5-FU, but in significantly less acute toxicity.

Radiation dose escalation for localized prostate cancer: intensity-modulated radiotherapy versus permanent transperineal brachytherapy.

BACKGROUND: In the current study, the effects of dose escalation for localized prostate cancer treatment with intensity-modulated radiotherapy (IMRT) or permanent transperineal brachytherapy (BRT) in comparison with conventional dose 3-dimensional conformal radiotherapy (3D-CRT) were evaluated. METHODS: This study included 853 patients; 270 received conventional dose 3D-CRT, 314 received high-dose IMRT, 225 received BRT, and 44 received external beam radiotherapy (EBRT) + BRT boost. The median radiation doses were 68.4 grays (Gy) for 3D-CRT and 75.6 Gy for IMRT. BRT patients received a prescribed dose of 144 Gy with iodine-125 (I-125) or 120 Gy with palladium-103 (Pd-103), respectively. Patients treated with EBRT + BRT received 45 Gy of EBRT plus a boost of 110 Gy with I-125 or 90 Gy with Pd-103. Risk group categories were low risk (T1-T2 disease, prostate-specific antigen level or=2 factors). RESULTS: With a median follow-up of 58 months, the 5-year biochemical control (bNED) rates were 74% for 3D-CRT, 87% for IMRT, 94% for BRT, and 94% for EBRT + BRT (P <.0001). For the intermediate-risk group, high-dose IMRT, BRT, or EBRT + BRT achieved significantly better bNED rates than 3D-CRT (P <.0001), whereas no improvement was noted for the low-risk group (P = .22). There was no increase in gastrointestinal (GI) toxicity from high-dose IMRT compared with conventional dose 3D-CRT, although there was more grade 2 genitourinary (GU) toxicity (toxicities were graded at the time of each follow-up visit using a modified Radiation Therapy Oncology Group [RTOG] scale). BRT caused more GU but less GI toxicity, whereas EBRT + BRT caused more late GU and GI toxicity than IMRT or 3D-CRT. CONCLUSIONS: The data from the current study indicate that radiation dose escalation improved the bNED rate for the intermediate-risk group. IMRT caused less acute and late GU toxicity than BRT or EBRT + BRT.

Adjuvant external beam radiation therapy with concurrent chemotherapy in the management of gallbladder carcinoma.

PURPOSE: This study was performed to evaluate the outcome of patients with gallbladder cancer who received postoperative concurrent chemotherapy and radiation therapy. METHODS AND MATERIALS: Curative resection followed by adjuvant combined modality therapy with external beam radiation therapy (EBRT) and chemotherapy was attempted in 21 consecutive gallbladder carcinoma (GBC) patients at the Mayo Clinic from 1985 through 1997. All patients received concurrent 5-fluorouracil during EBRT. EBRT fields encompassed the tumor bed and regional lymph nodes (median dose of 54 Gy in 1.8-2.0-Gy fractions). One patient received 15 Gy intraoperatively after EBRT. A retrospective analysis was performed for the end points of local control, distant failure, and overall survival. RESULTS: After maximal resection, 12 patients had no residual disease on pathologic evaluation, 5 had microscopic residual disease, and 4 had gross residual disease. One patient had Stage I disease, and 20 had Stage III-IV disease. With median follow-up of 5 years (range: 2.6-11.5 years), 5-year survival for the entire cohort was 33%. The 5-year survival rate of patients with Stage I-III disease was 65% vs. 0% for those with Stage IV disease (p < 0.02). For patients with no residual disease, 5-year survival was 64% vs. 0% for those with residual disease (p = 0.002). The median survival was 0.6, 1.4, and 5.1 years for patients with gross residual, microscopic residual, and no residual disease, respectively (p = 0.02). The 5-year local control rate for the entire cohort was 73%. Two-year local control rates were 0%, 80%, and 88% for patients with gross residual, microscopic residual, or no residual disease, respectively (p < 0.01). Five-year local control rates were 100% for the 6 patients who received total EBRT doses >54 Gy (microscopic residual, 3 patients; gross residual, 1 patient; negative but narrow margins, 2 patients) vs. 65% for the 15 who received a lower dose (3, gross residual; 2, microresidual; 10, negative margins). CONCLUSION: Patients with completely resected (negative margins) GBC followed by adjuvant EBRT plus 5-fluorouracil chemotherapy had a relatively favorable prognosis, with a 5-year survival rate of 64%. These results seem to be superior to historical surgical controls from the Mayo Clinic and other institutions, which report 5-year survival rates of approximately 33% with complete resection alone. Both tumor stage and extent of resection seemed to influence survival and local control. More aggressive measures using current cancer therapies and integration of new cancer treatment modalities will be required to favorably impact on the poor prognosis of patients with Stage IV or subtotally resected GBC. Additional investigation leading to earlier diagnosis is warranted, because most patients with GBC present with advanced disease.