Re-irradiation and hyperthermia after surgery for recurrent breast cancer.

PURPOSE: Evaluation of efficacy and side effects of combined re-irradiation and hyperthermia electively or for subclinical disease in the management of locoregional recurrent breast cancer. METHODS AND MATERIALS: Records of 198 patients with recurrent breast cancer treated with re-irradiation and hyperthermia from 1993 to 2010 were reviewed. Prior treatments included surgery (100%), radiotherapy (100%), chemotherapy (42%), and hormonal therapy (57%). Ninety-one patients were treated for microscopic residual disease following resection or systemic therapy and 107 patients were treated electively for areas at high risk for local recurrences. All patients were re-irradiated to 28-36Gy (median 32) and treated with 3-8 hyperthermia treatments (mean 4.36). Forty percent of the patients received concurrent hormonal therapy. Patient and tumor characteristics predictive for actuarial local control (LC) and toxicity were studied in univariate and multivariate analysis. RESULTS: The median follow-up was 42months. Three and 5year LC-rates were 83% and 78%. Mean of T90 (tenth percentile of temperature distribution), maximum and average temperatures were 39.8°C, 43.6°C, and 41.2°C, respectively. Mean of the cumulative equivalent minutes (CEM43) at T90 was 4.58min. Number of previous chemotherapy and surgical procedures were most predictive for LC. Cumulative incidence of grade 3 and 4 late toxicity at 5years was 11.9%. The number of thermometry sensors and depth of treatment volume were associated with acute hyperthermia toxicity. CONCLUSIONS: The combination of re-irradiation and hyperthermia results in a high LC-rate with acceptable toxicity.

The tolerance of reirradiation and hyperthermia in breast cancer patients with reconstructions.

BACKGROUND: Breast cancer recurrences in previously irradiated areas are treated with reirradiation (reRT) and hyperthermia (HT). The aim of this retrospective study is to quantify the toxicity of HT in breast cancer patients with reconstruction. METHODS: Between 1992 and 2009, 36 patients were treated with reRT with a scheme of 8 fractions of 4.0 Gy in 4 weeks, and HT on a total of 37 tissue reconstructions. The types of reconstructions were: split-thickness skin graft (15), transverse rectus abdominis myocutaneous flap (1), latissimus dorsi flap (14), rhomboid flap (1) or a combination of grafts and flaps (6). Toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Patient, tumour, and treatment characteristics predictive for the endpoints were identified in univariate and multivariate analyses. The primary endpoint was HT toxicity. Secondary endpoints were acute and late radiotherapy (RT) toxicity, complete response (CR), local control (LC) and overall survival (OS). RESULTS: The median follow-up time was 64 months. Grade 2 HT toxicity occurred in four patients and grade 3 in three. The three patients with grade 3 HT toxicity required reoperation. None of the evaluated parameters showed a significant relationship with HT toxicity. The CR rate in 15 patients with macroscopic disease was 80%. The 3 and 5 year LC rates were 74% and 69%; the median OS was 55 months. CONCLUSIONS: Combined reRT and HT in breast cancer patients with reconstruction is safe and effective.

Complications in wound healing after chest wall resection in cancer patients; a multivariate analysis of 220 patients.

BACKGROUND: Extensive chest wall resections can provoke a wide variety of complications, in particular, complicated wound healing. A lower complication rate will be achieved when local factors contributing to wound healing can be identified and improved. The aim of this study is to describe these factors, irrespective of prognosis, survival, or systemic complications. METHODS: Retrospectively, the files of all patients undergoing an extended chest wall resection in a single institute during a 20-year period were retrieved. Patient demographics, use of preoperative therapy, tumor histology, the type of prosthesis (if any), and postoperative wound complications were recorded. Univariate and multivariate analysis were performed to identify factors contributing significantly to wound healing problems. RESULTS: From January 1987 to December 2006, 220 patients underwent a chest wall resection, defined as resection of at least one rib, and/or part of the sternum. In 145 patients (66%) this procedure was uneventful. Multivariate analysis showed that ulceration of tumor and the use of omentum for soft tissue reconstruction comprised independent factors contributing to impaired wound healing. CONCLUSION: Several factors leading to wound healing problems exist preoperatively. In a multidisciplinary setting, these factors should be weighed carefully against the possible benefits of an extended chest wall resection. Especially when ulceration of a tumor exists, or when omentum is considered for soft tissue reconstruction, increased risk on wound healing problems occurs. For the majority of patients chest wall resection will remain a safe and suitable procedure.

Outcome after surgical resections of recurrent chest wall sarcomas.

PURPOSE: Sarcomas of the chest wall are rare, and wide surgical resection is generally the cornerstone of treatment. The objective of our study was to evaluate outcome of full-thickness resections of recurrent and primary chest wall sarcomas. PATIENTS AND METHODS: To evaluate morbidity, mortality, and overall and disease-free survival after surgical resection of primary and recurrent chest wall sarcomas, we performed a retrospective review of all patients with sarcomas of the chest wall surgically treated at two tertiary oncologic referral centers between January 1980 and December 2006. Patient, tumor, and treatment characteristics, as well as the follow-up of these patients, were retrieved from the patients' original records. RESULTS: One hundred twenty-seven patients were included in this study, 83 patients with a primary sarcoma and 44 patients with a recurrence. Age, sex, tumor size, histologic type, grade and localization on the chest wall were similar for both groups. Fewer neoadjuvant and adjuvant therapies were used in the treatment of recurrences. Chest wall resection was more extensive in the recurrent group, which did not result in more complications (23%) or more reinterventions (5%). Microscopically radical resection was achieved in 80% of the primary sarcomas and 64% of the recurrences. With a median follow-up of 73 months, disease-free survival after surgery for recurrences was 18 months versus 36 months for primary sarcomas, with 5-year survival rates of 50% and 63%, respectively. CONCLUSION: Although chances for local control are lower after surgical treatment of recurrent chest wall sarcoma, chest wall resection is a safe and effective procedure, with an acceptable survival.

Prophylactic mastectomy in BRCA1/2 mutation carriers and women at risk of hereditary breast cancer: long-term experiences at the Rotterdam Family Cancer Clinic.

BACKGROUND: BRCA1/2 mutation carriers and women from a hereditary breast(/ovarian) cancer family have a highly increased risk of developing breast cancer (BC). Prophylactic mastectomy (PM) results in the greatest BC risk reduction. Long-term data on the efficacy and sequels of PM are scarce. METHODS: From 358 high-risk women (including 236 BRCA1/2 carriers) undergoing PM between 1994 and 2004, relevant data on the occurrence of BC in relation to PM, complications in relation to breast reconstruction (BR), mutation status, age at PM and preoperative imaging examination results were extracted from the medical records, and analyzed separately for women without (unaffected, n = 177) and with a BC history (affected, n = 181). RESULTS: No primary BCs occurred after PM (median follow-up 4.5 years). In one previously unaffected woman, metastatic BC was detected almost 4 years after PM (primary BC not found). Median age at PM was younger in unaffected women (P < .001), affected women more frequently were 50% risk carriers (P < .001). Unexpected (pre)malignant changes at PM were found in 3% of the patients (in 5 affected, and 5 unaffected women, respectively). In 49.6% of the women opting for BR one or more complications were registered, totaling 215 complications, leading to 153 surgical interventions (71%). Complications were mainly related to cosmetic outcome (36%) and capsular formation (24%). CONCLUSIONS: The risk of developing a primary BC after PM remains low after longer follow-up. Preoperative imaging and careful histological examination is warranted because of potential unexpected (pre)malignant findings. The high complication rate after breast reconstruction mainly concerns cosmetic issues.

Satisfaction with prophylactic mastectomy and breast reconstruction in genetically predisposed women.

BACKGROUND: Prophylactic mastectomy with breast reconstruction is a risk-reducing strategy for women at increased risk of breast cancer. It remains a very radical intervention, and long-term data on satisfaction are insufficiently available. In the present follow-up study, the authors assess satisfaction with prophylactic mastectomy and breast reconstruction and its impact on sexual relationships. METHODS: The authors conducted a retrospective study using a short self-report questionnaire administered to 114 genetically predisposed women who underwent prophylactic mastectomy and breast reconstruction mainly by subpectorally implanted silicone prostheses performed at one institution. RESULTS: The median follow-up time between prophylactic mastectomy/breast reconstruction and completion of the questionnaire was 3 years. Sixty percent of all participants were satisfied with the result of prophylactic mastectomy/breast reconstruction. Satisfaction was significantly and negatively correlated with perceived lack of information, experienced complications, ongoing complaints, whether or not the reconstructed breasts feel "like your own," and not choosing this type of breast reconstruction again. Adverse effects in the patient's sexual relationship were strongly correlated with perceived lack of information, discrepant expectations, ongoing complaints and limitations, whether or not the reconstructed breasts feel "like your own," altered feelings of femininity, partner's negative perception on femininity and sexuality, and not choosing this type of breast reconstruction again. CONCLUSIONS: A majority of women would choose the procedure again, but adverse effects and untoward changes in the perception of the sexual relationship need to be addressed in the counselling of women at high risk, to optimize an informed choice and enable adequate adjustment postoperatively.

Pathological internal mammary lymph nodes in secondary and tertiary deep inferior epigastric perforator flap breast reconstructions.

Use of internal mammary vessels during breast reconstruction provides information on part of the internal mammary chain lymph nodes (LNs). It was evaluated whether our current practice of screening should be changed to identify those delayed breast reconstruction patients with tumor-positive internal mammary nodes (IMNs) and whether breast reconstruction should be continued, in case suspicious IMNs were found intraoperatively. From February 2002 to December 2004, 81 patients had received 98 deep inferior epigastric perforator flaps for delayed breast reconstruction. Prospectively collected data for suspicious internal mammary LNs were evaluated. In 13 patients (16%) who had received a delayed breast reconstruction, macroscopically suspicious LNs were detected in the course of the internal mammary chain. Three patients (4%) had a pathologic diagnosis of malignancy, which was found to match their primary tumor. No relationship between positive internal mammary chain LNs and location of the primary tumor, TNM-stage, or previously administered adjuvant therapy was found. Suspicious internal mammary chain LNs found during recipient vessel dissection for breast reconstruction can have important consequences for treatment of malignant disease in individual patients. Presented data do not support changing the current perioperative approach of delayed breast reconstruction.

Mastectomy by inverted drip incision and immediate reconstruction: data from 510 cases.

BACKGROUND: Immediate reconstruction of the breast can be performed in selected cases after mastectomy for breast cancer or after prophylactic mastectomy in patients with a high risk of developing breast cancer. Despite the frequency with which these procedures are performed, data from large series of subpectoral implantation of silicone prostheses in combination with a skin-saving approach are lacking. METHODS: In this retrospective study, data on complications and late surgical interventions in 356 patients who underwent 510 mastectomies with an inverted drip incision and immediate reconstruction (MIDIIR) were analyzed to determine potential prognostic factors of early complications. RESULTS: In 82% of the MIDIIRs, the postoperative course was uneventful. In 18%, the complications were infection (32 cases), necrosis of the skin flap (29 cases), bleeding (31 cases), and protrusion of the prosthesis (20 cases), resulting in surgery in 9, 12, 15, and 20 cases, respectively. At the end of the follow-up period, 30 (6%) prostheses were definitively removed. Age, size of the prostheses, radiotherapy, previous lumpectomy, and indication for mastectomy were not significant factors for the prognosis of early complications. CONCLUSIONS: With the right technique and indications, MIDIIR is a very safe procedure and should be one of the surgical treatments that can be offered in the overall management of patients with, or at high risk for, breast cancer.

Factors Influencing Prognosis After Initial Inadequate Excision (IIE) for Soft Tissue Sarcoma.

Purpose. The influence of initial inadequate excision (IIE) of soft tissue sarcoma (STS) on local control and overall survival is not well established. It is generally believed that an IIE may have a negative impact on both, despite subsequent treatment by radical surgery and radiotherapy. However, data on local recurrence-free survival/overall survival are conflicting and there are no data on the effect of IIE on overall survival.Patients and methods. A retrospective analysis was made of 86 patients with soft tissue sarcoma of the extremities and trunk after an IIE had been performed due to inappropriate work-up. The minimal follow-up was 7 years. Specimens of the subsequent radical resection were evaluated for residual tumor, grade of tumor and complications of IIE. Endpoints were recurrence-free survival and overall survival.Results. Specimens of the subsequent radical resection showed residual tumor in 66 patients (77%). The most common complication after IIE was hematoma. In both univariate and multivariate analyses, grade II/III tumors and complications after IIE are significant negative prognostic factors for local recurrence-free survival (P = 0.008 and P = 0.002, respectively, in the Cox model). For this survival, three prognostic groups could be formed based on grade, or presence or absence of complications. Adjuvant radiotherapy did not change the rate of local recurrence-free survival. For overall survival, only tumor grade is a significant factor (log-rank test).Conclusion. This retrospective study shows that complications associated with an IIE have a significant negative effect on local control, but not on overall survival, because IIE is often the result of inappropriate work-up before surgery. For better diagnosis and therapy STS should be treated in specialized centers.

Determination of the molecular relationship between multiple tumors within one patient is of clinical importance.

PURPOSE: To determine the molecular relationship between multiple tumors within one patient and to evaluate the impact of this knowledge on clinical management. PATIENTS AND METHODS: In 25 consecutive patients with multiple tumors, proven by histology and immunohistochemistry to be identical, molecular aberrations were determined. Each patient had at least one lesion in the lung or head and neck region. Loss of heterozygosity (LOH) and p53 aberration analyses were carried out, and similar aberration profiles suggest clonality and metastasis whereas different profiles suggest independent primary tumors. RESULTS: The molecular determinations indicated that 12 patients had a probable second primary tumor and 10 patients had a metastasis of the first lesion. In three patients, both an independent primary tumor and a metastasis were present. The molecular findings determined the course of additional treatment in all 10 patients with metastases, in all three patients with both a second primary tumor and a metastasis, and in seven of 12 patients with a second primary tumor. CONCLUSION: By comparing DNA alterations of multiple tumors within one patient, the relationship between the tumors can be assessed. This study shows that in 20 of 25 patients, knowledge of the nature of both lesions was essential in clinical decision making. Furthermore, after thorough analysis of the five cases where clinical decision making was not influenced, there was in retrospect no clear indication for LOH or p53 analysis. Because these molecular analyses can be performed on routine specimens, they can be applied in almost all patients.