Patient preferences regarding intraoperative versus external beam radiotherapy for early breast cancer and the impact of socio-demographic factors.

PURPOSE: Patient comfort and preference have steadily gained attention in radio-oncologic treatment of breast cancer. Therefore, the purpose of this investigation was to further explore patient preferences in choosing between intraoperative radiotherapy (IORT) and external beam radiotherapy (EBRT). METHODS: We prospectively analysed data of 101 women, who were candidates for breast-conserving surgery with adjuvant radiotherapy. A two-part video was shown to patients: an educational section about EBRT/IORT, followed by a preference elicitation section focusing on additional accepted risk (AAR) of recurrence after either treatment. Furthermore, participants completed a questionnaire to identify factors that influence patient preference of radiation modality. RESULTS: The data demonstrate that 42.5% of patients would accept additional risk of recurrence for IORT versus 9% AAR for EBRT, while 48.5% of patients would not accept any additional risk, yet would choose IORT over EBRT if risks of recurrence were equivalent. When combining patient preferences and the results from the questionnaire, no single socio-economic/-demographic factor was found to significantly correlate with AAR of IORT. CONCLUSION: Our study confirms the existence of subgroups of breast cancer patients who would accept an additional risk of recurrence associated with choice of radiation modality to receive a single dose of IORT as adjuvant radiotherapy for breast cancer instead of EBRT over several weeks; yet our data fail to identify a single factor significantly associated with these patient preferences and, therefore, helpful for individualised decision-making processes.

Patient Preferences Regarding Chemotherapy in Metastatic Breast Cancer-A Conjoint Analysis for Common Taxanes.

Background: The purpose of this investigation was to explore patient perception regarding the importance of efficacy, toxicity, and logistics in the choice of regimen of taxane-based chemotherapy (CHT) for patients with metastatic breast cancer (MBC). Methods: This dual-center study analyzed data of 100 women diagnosed with MBC, who were asked for their preferences regarding chemotherapy by means of conjoint analysis. Included attributes were progression free survival (PFS), application form, time and frequency, need of premedication, risk of alopecia, fatigue, febrile neutropenia, and neuropathy. Furthermore, participants completed a questionnaire about their personal and medical history. Regression analyses were performed to identify factors that influence patient preference in terms of specific treatment choice. Results: Of 8 attributes, severe neutropenia was top priority for the majority of patients, followed by alopecia, neuropathy and PFS. When combining these patient preferences and the results of the questionnaire, patients' age as, well as, relationship status had significant impact on the importance of PFS. Moreover, longer travel time to the treatment center was significantly associated with preferences regarding PFS. Ranking by combination of respective part-worth values demonstrated nab-paclitaxel to be favored over paclitaxel and docetaxel. Conclusion: Side effects of CHT and PFS prove to be critical factors for patients affecting choice of treatment in MBC with severe neutropenia being top priority, followed by alopecia, neuropathy, and PFS. Age, commute time, and relationship status were identified as significant determinants of patient preference. Total utility calculation by combination of part-worth values ranked nab-paclitaxel as the most preferable taxane.

Impact of Tumor Localization and Method of Preoperative Biopsy on Sentinel Lymph Node Mapping After Periareolar Nuclide Injection.

BACKGROUND: To evaluate whether tumor localization and method of preoperative biopsy affect sentinel lymph node (SLN) detection after periareolar nuclide injection in breast cancer patients. METHODS AND FINDINGS: 767 breast cancer patients were retrospectively included. For lymphscintigraphy periareolar nuclide injection was performed and the SLN was located by gamma camera. Patient and tumor characteristics were correlated to the success rate of SLN mapping. SLN marking failed in 9/61 (14.7%) patients with prior vacuum-assisted biopsy and 80/706 (11.3%) patients with prior core needle biopsy. Individually evaluated, biopsy method (p = 0.4) and tumor localization (p = 0.9) did not significantly affect the SLN detection rate. Patients with a vacuum-assisted biopsy of a tumor in the upper outer quadrant had a higher odds ratio of failing in SLN mapping (OR 3.8, p = 0.09) compared to core needle biopsy in the same localization (OR 0.9, p = 0.5). CONCLUSIONS: Tumor localization and preoperative biopsy method do not significantly impact SLN mapping with periareolar nuclide injection. However, the failure risk tends to rise if vacuum-assisted biopsy of a tumor in the upper outer quadrant is performed.

Does physical activity improve quality of life in cancer patients undergoing chemotherapy?

BACKGROUND: Improved cancer treatments have resulted in prolonged survival. Nevertheless, tumor symptoms and side effects still compromise physical activity and quality of life (QoL). PATIENTS AND METHODS: We conducted an anonymous survey among cancer patients undergoing chemotherapy using standardized questionnaires: the 'Freiburger Fragebogen zur körperlichen Aktivität' (Freiburg Questionnaire on Physical Activity) and European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. Two main questions were addressed: were there differences (1) in physical activity and QoL between patients who do not believe that sport could improve their QoL and those who believe it could (group A vs. B); and (2) in QoL between patients with a total activity (TA) < 18 metabolic equivalent of task (MET) h/week and those with a TA of ≥ 18 MET h/week (group C vs. D)? RESULTS: 276 of 400 questionnaires were completed. Groups A and B were balanced in terms of baseline characteristics. Group A suffered significantly more from fatigue and pain; group B reported higher levels of global health status (GHS) and TA. Groups C and D differed in gender distribution, age, and educational background. Group D had significantly higher levels of GHS, group C suffered more from fatigue, pain, and appetite loss. CONCLUSION: Physical activity correlates with a better QoL of cancer patients undergoing chemotherapy.

Improvements in health-related quality of life by comprehensive cancer pain therapy: a pilot study with breast cancer outpatients under palliative chemotherapy.

BACKGROUND: Cancer-related pain is highly prevalent among outpatients with metastatic breast cancer affecting their health-related quality of life (HRQoL). This study evaluates potential effects of comprehensive pharmacologic cancer pain therapy (CPT) on HRQoL. PATIENTS AND METHODS: 52 outpatients with metastatic breast cancer undergoing palliative chemotherapy participated. 28 patients suffering from moderate to severe cancer pain were offered CPT. 13 patients participated (intervention group), and 15 declined participation (control group). HRQoL was assessed with the Quality of Life Questionnaire (EORTC QLQ-C30) and the breast module QLQ-BR23 at baseline and after 3 weeks. RESULTS: At baseline, 83% of the patients experienced cancer-related pain, of whom 35% were not prescribed any pain medication. HRQoL of all patients was reduced compared to reference scores. After CPT, the intervention group reported significantly alleviated pain and improvement in several HRQoL subscales (Global QoL, Emotional Functioning, Physical Functioning, Future Perspective, Sleeplessness). The control group did not change significantly. CONCLUSION: This study emphasizes the demand for sufficient pain management in palliative breast cancer outpatients. The combination of CPT as a guidance for the pharmacological aspects of cancer pain management and the EORTC QLQ-C30 as an assessment and surveillance tool appears to be a method that warrants further research.

A cohort analysis to identify eligible patients for intraoperative radiotherapy (IORT) of early breast cancer.

BACKGROUND: Since the results from the randomized TARGIT A trial were published, intraoperative radiotherapy (IORT) is used more often. IORT can be provided as accelerated partial breast irradiation (APBI) or as a boost. The definition of suitable patients for IORT as APBI differs between different national societies (e.g. ESTRO and ASTRO) and different inclusion criteria of trials and so does the eligibility of patients. This analysis identifies eligible patients for IORT according to available consensus statements and inclusion criteria of the ongoing TARGIT trials. METHODS: Between 01/03 - 12/09, 1505 breast cancer cases were treated at the breast cancer center at the University Medical Center Mannheim. Complete data sets for age, stage (T, N, and M), histology and hormone receptor status were available in 1108 cases. Parameters to identify eligible patients are as follows: ESTRO: >50 years, invasive ductal carcinoma/other favorable histology (IDC), T1-2 (≤3 cm), N0, any hormone receptor status, M0; ASTRO: ≥60 years, IDC, T1, N0, positive estrogen hormone receptor status, M0; TARGIT E "elderly", risk adapted radiotherapy with IORT followed by external beam radiotherapy in case of risk factors in final histopathology, phase II: ≥70 years, IDC, T1, N0, any hormone receptor status, M0; TARGIT C "consolidation", risk adapted radiotherapy, phase IV: ≥50 years, IDC, T1, N0, positive hormone receptor status, M0; TARGIT BQR "boost quality registry": every age, every histology, T1-2 (max. 3.5 cm), any hormone receptor status, N0/+, M0/+. RESULTS: Out of the 1108 cases, 379 cases (34.2%) were suitable for IORT as APBI regarding the ESTRO and 175 (15.8%) regarding the ASTRO consensus statements. 82 (7.4%) patients were eligible for the TARGIT E trial, 258 (23.3%) for the TARGIT C trial and 671 (60.6%) for the TARGIT BQR registry. According to the consensus statements of ASTRO (45.1%) and ESTRO (41.4%) about half of the eligible patients were treated with IORT as APBI. From the eligible patients fulfilling the criteria for IORT boost (35%) about one third was eventually treated. CONCLUSIONS: Patient selection for IORT should be restrictive. For IORT as APBI the TARGIT trials are even more restrictive including patients than the ESTRO and ASTRO consensus statements.

Pure natural orifice transluminal endoscopic surgery (NOTES) involving peroral endoscopic salpingo-oophorectomy (POESY).

OBJECTIVE: Natural orifice transluminal endoscopic surgery (NOTES) is a surgical approach that uses natural orifices to gain access to areas of the body. In the present article, we describe the first transgastric pure NOTES salpingo-oophorectomy, which we call peroral endoscopic salpingo-oophorectomy (POESY). METHODS: A woman with BRCA1 mutation presented for prophylactic bilateral salpingo-oophorectomy. We offered her the transgastric approach, having performed more than 25 transgastric appendectomies. After gastroscopic incision in the corpus wall, we advanced the gastroscope into the abdominal cavity. Salpingo-oophorectomy was performed with the help of an intrauterine manipulator and a transvaginally introduced 5-mm trocar. The posterior colpotomy was dilated and the specimens were extracted. The gastrotomy was closed with an over-the-scope clip, and the colpotomy with a running suture. RESULTS: The gastroscope provided excellent optical control and good tissue preparation. Prophylactic bilateral salpingo-oophorectomy was performed successfully via POESY. The patient recovered quickly and was discharged on the third day, with an uneventful follow-up. CONCLUSION: The present case demonstrates the feasibility of transgastric access. The gastroscope provided excellent optical control and good tissue preparation. Therefore, we expect an increasing role of transgastric procedures for diseases in the pelvic region, particularly if new endoscopic platforms with better means of instrumentation and tissue management become available.

Cancer patients and advance directives: a survey of patients in a hematology and oncology outpatient clinic.

BACKGROUND: In 2009, Germany enacted a new law supporting advance directives that led to heated discussions in the media and the public. 3 years after the law passed, we surveyed patients with malignant diseases with regards to their views on advance directives. PATIENTS AND METHODS: Between September 2011 and July 2012 an anonymous survey on advance directives was conducted among 617 patients at the hematology and oncology outpatient department of the University Hospital Mannheim, using a standardized questionnaire developed for this investigation. RESULTS: Of the 503 patients who returned the questionnaire, 31% (n = 157) indicated having an advance directive. Of these 157, 54% (n = 85) completed the advance directive after 2009. 56% (282 out of 503) desired more information on advance directives. Of these, 71% (201 out of 282) wanted their general physician and 45% (128 out of 282) their specialist, to provide more information about this issue. Of the 339 patients without an advance directive, 47% (n = 158) stated that they had 'not worried about that yet'. CONCLUSION: Although the percentage of patients with advance directives has increased since the legislative amendment, more information is still required by patients. It is recommended that physicians should discuss advance directives more frequently with their patients.

Radiation-related quality of life parameters after targeted intraoperative radiotherapy versus whole breast radiotherapy in patients with breast cancer: results from the randomized phase III trial TARGIT-A.

BACKGROUND: Intraoperative radiotherapy (IORT) is a new treatment approach for early stage breast cancer. This study reports on the effects of IORT on radiation-related quality of life (QoL) parameters. METHODS: Two hundred and thirty women with stage I-III breast cancer (age, 31 to 84 years) were entered into the study. A single-center subgroup of 87 women from the two arms of the randomized phase III trial TARGIT-A (TARGeted Intra-operative radioTherapy versus whole breast radiotherapy for breast cancer) was analyzed. Furthermore, results were compared to non-randomized control groups: n = 90 receiving IORT as a tumor bed boost followed by external beam whole breast radiotherapy (EBRT) outside of TARGIT-A (IORT-boost), and n = 53 treated with EBRT followed by an external-beam boost (EBRT-boost). QoL was collected using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires C30 (QLQ-C30) and BR23 (QLQ-BR23). The mean follow-up period in the TARGIT-A groups was 32 versus 39 months in the non-randomized control groups. RESULTS: Patients receiving IORT alone reported less general pain (21.3 points), breast (7.0 points) and arm (15.1 points) symptoms, and better role functioning (78.7 points) as patients receiving EBRT (40.9; 19.0; 32.8; and 60.5 points, respectively, P < 0.01). Patients receiving IORT alone also had fewer breast symptoms than TARGIT-A patients receiving IORT followed by EBRT for high risk features on final pathology (IORT-EBRT; 7.0 versus 29.7 points, P < 0.01). There were no significant differences between TARGIT-A patients receiving IORT-EBRT compared to non-randomized IORT-boost or EBRT-boost patients and patients receiving EBRT without a boost. CONCLUSIONS: In the randomized setting, important radiation-related QoL parameters after IORT were superior to EBRT. Non-randomized comparisons showed equivalent parameters in the IORT-EBRT group and the control groups.

Late radiation toxicity after intraoperative radiotherapy (IORT) for breast cancer: results from the randomized phase III trial TARGIT A.

The randomized phase III trial TARGIT A showed non-inferiority regarding local control after intraoperative radiotherapy (IORT 20 Gy which was followed by whole breast radiotherapy (WBRT) in patients with risk factors only) in comparison to standard WBRT (50-56 Gy) after breast-conserving surgery in selected patients. This is the first analysis of long-term toxicities in the setting of TARGIT. Between 02/2002 and 12/2008, 305 patients were treated within TARGIT A (Arm A: n = 34 IORT, n = 20 IORT + WBRT for risk factors; Arm B WBRT: n = 55) or received IORT as a planned boost (control group: n = 196) at a single center. Toxicity was assessed according to the LENT SOMA scales. No significant differences were seen between Arm A and Arm B regarding fibrosis, breast edema, retraction, ulceration, lymphedema, hyperpigmentation, and pain. Arm A had significantly less telangiectases compared to Arm B (p = 0.049). In the subanalysis (Arm A IORT vs. Arm A IORT + WBRT vs. Arm B), fibrosis had a cumulative rate of 5.9 versus 37.5 versus 18.4 %, respectively (38.2 % IORT boost control group), at 3 years. No telangiectases were seen after IORT alone (0 % Arm A IORT vs. 17.5 % Arm A IORT + WBRT vs. 17.7 % Arm B). The hazard ratio of higher grade toxicity as first event was 0.46 (95 % CI, 0.26-0.83) for Arm A IORT as compared to Arm B (p = 0.010). No recurrences were seen after a median follow-up of 40 months (Arm A) and 42 months (Arm B). With its very low chronic skin toxicity rates and outstanding long-term results regarding toxicity and local control, IORT with 50 kV X-rays is a safe and effective method for treatment of selected breast cancer patients.

Intraoperative radiotherapy during breast-conserving surgery using a miniature x-ray generator (Intrabeam®): theoretical and experimental background and clinical experience.

Breast cancer is currently the most frequent indication for intraoperative radiotherapy with increasing numbers worldwide. Intraoperative radiotherapy can be used as a tumor bed boost followed by whole breast radiotherapy, or as a distinct form of accelerated partial breast irradiation in selected patients. This article summarizes the theoretical background including pattern of recurrence and distribution of tumor cell foci in the breast and discusses the rationale for intraoperative radiotherapy, especially using a miniature x-ray generator (Intrabeam(®)). The concepts of how to avoid geographic and temporal miss by giving radiotherapy during surgery to the open wound cavity are described. Experimental and clinical experience is presented based on in vitro experiments and more than 300 treated patients in a single department with mature follow-up.

Tissue expression and sero-reactivity of tumor-specific antigens in colorectal cancer.

The expression of 14 individual and two groups of tumor antigens was characterized for colorectal carcinoma by RT-PCR using 26 colorectal carcinoma specimens, eight cell lines, six samples of patients with inflammatory bowl diseases, and nine specimens from different locations of an individual patient with a metastasized rectal carcinoma. The most frequently detected mRNAs were MAGE-A1 (58%), GAGE-3-7 (54%), and cTAGE-5a (31%). At medium frequencies (12-19%) we found cTAGE-1, MAGE-A2, se57-1, RAGE-4, and GAGE-1,2,8, while other tumor antigens were expressed rarely (<9%). 85% of the samples were positive for at least one of the most frequently expressed antigens. Using a secondary SEREX approach and sera of eight colorectal cancer patients we found reactive antibodies against recombinant cTAGE-1 (2 sera), se57-1 (2), truncated GAGE (1), and MAGE-A1 (1). We conclude that certain cancer-germline genes can be detected in colorectal cancer and might therefore be promising targets for immunotherapy.