Mehran Habibi

Detection of Cancer DNA in Plasma of Patients with Early-Stage Breast Cancer

Purpose: Detecting circulating plasma tumor DNA (ptDNA) in patients with early-stage cancer has the potential to change how oncologists recommend systemic therapies for solid tumors after surgery. Droplet digital polymerase chain reaction (ddPCR) is a novel sensitive and specific platform for mutation detection. Experimental Design: In this prospective study, primary breast tumors and matched pre- and postsurgery blood samples were collected from patients with early-stage breast cancer (n = 29). Tumors (n = 30) were analyzed by Sanger sequencing for common PIK3CA mutations, and DNA from these tumors and matched plasma were then analyzed for PIK3CA mutations using ddPCR. Results: Sequencing of tumors identified seven PIK3CA exon 20 mutations (H1047R) and three exon 9 mutations (E545K). Analysis of tumors by ddPCR confirmed these mutations and identified five additional mutations. Presurgery plasma samples (n = 29) were then analyzed for PIK3CA mutations using ddPCR. Of the 15 PIK3CA mutations detected in tumors by ddPCR, 14 of the corresponding mutations were detected in presurgical ptDNA, whereas no mutations were found in plasma from patients with PIK3CA wild-type tumors (sensitivity 93.3%, specificity 100%). Ten patients with mutation-positive ptDNA presurgery had ddPCR analysis of postsurgery plasma, with five patients having detectable ptDNA postsurgery. Conclusions: This prospective study demonstrates accurate mutation detection in tumor tissues using ddPCR, and that ptDNA can be detected in blood before and after surgery in patients with early-stage breast cancer. Future studies can now address whether ptDNA detected after surgery identifies patients at risk for recurrence, which could guide chemotherapy decisions for individual patients. Clin Cancer Res; 20(10); 2643–50. ©2014 AACR.

Conditioning neoadjuvant therapies for improved immunotherapy of cancer

Recent advances in the treatment of melanoma and non-small cell lung cancer (NSCLC) by combining conventional therapies with anti-PD1/PD-L1 immunotherapies, have renewed interests in immunotherapy of cancer. The emerging concept of conventional cancer therapies combined with immunotherapy differs from the classical concept in that it is not simply taking advantage of their additive anti-tumor effects, but it is to use certain therapeutic regimens to condition the tumor microenvironment for optimal response to immunotherapy. To this end, low dose immunogenic chemotherapies, epigenetic modulators and inhibitors of cell cycle progression are potential candidates for rendering tumors highly responsive to immunotherapy. Next generation immunotherapeutics are therefore predicted to be highly effective against cancer, when they are used following appropriate immune modulatory compounds or targeted delivery of tumor cell cycle inhibitors using nanotechnology.

Predictors of radiation-induced acute skin toxicity in breast cancer at a single institution: Role of fractionation and treatment volume

Purpose The associations among radiation fractionation, body mass index (BMI), and acute skin toxicity with adjuvant radiation for breast cancer is of increasing interest. This study evaluated the rate of grade ≥2 dermatitis and moist desquamation (MD) in patients with a high BMI who were treated to the breast or chest wall to understand the role of radiation target, fractionation regimen, and BMI. Methods and materials We retrospectively evaluated 280 patients treated with adjuvant radiation for breast cancer after up-front surgery. We collected information on patient demographics, disease and treatment characteristics, and acute skin toxicities. Multiple logistic regression models were used to evaluate for predictors of grade ≥2 dermatitis and MD. Results Patients undergoing post-mastectomy radiation therapy (PMRT) had the highest rate of MD (24%). The rate was lower (8.7%) among lumpectomy patients, but those receiving conventional fractionation had a higher rate of MD (10.9%) compared with hypofractionated therapy (1.8%; P = .05). Among lumpectomy patients, chemotherapy use (odds ratio, 3.74; P = .04) and regional nodal irradiation (odds ratio, 3.29; P = .03) were also significant predictors of MD. Despite an elevated average BMI among lumpectomy patients, hypofractionated therapy resulted in lower rates of skin toxicity. Conclusions We identified multiple risk factors for acute skin toxicity, including the use of PMRT and conventionally fractionated regimens. Elevated BMI, regional nodal irradiation, and chemotherapy use were associated with an increased risk of MD. Our findings highlight the need to explore the use of less toxic hypofractionated regimens in patients who are at the highest risk of acute skin toxicity, including those with a higher BMI and those receiving PMRT.

Combined modality therapy improves overall survival for angiosarcoma

Colette J. Shen, Aaron S. Parzuchowski, Megan N. Kummerlowe, Carol D. Morris, Christian F. Meyer, Mehran Habibi, Deborah A. Frassica, Adam S. Levin, Katherine A. Thornton and Stephanie A. Terezakis Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Hospital, Baltimore, MD, USA; Department of Orthopaedic Surgery, Johns Hopkins Hospital, Baltimore, MD, USA; Department of Oncology, Johns Hopkins Hospital, Baltimore, MD, USA; Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA; Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

Oncoplastic Breast Reconstruction: Should All Patients be Considered?

Oncoplastic surgery of the tissue defect from partial mastectomy should be considered for all patients. It can result in in significant asymmetries from scar contraction, skin tethering, and alterations in the nipple areolar complex location. Indications, risks, and benefits are discussed. Optimal procedures are described, considering resected specimen volume, primary tumor location, tumor to breast size ratio, and the impact on the nipple areolar complex. Indications for plastic surgery consultation and joint surgery are discussed. Surgical management includes incision planning, preservation of the nipple areolar complex pedicle and position, patient positioning, incision location, and recovery.

Opioid-Prescribing Guidelines for Common Surgical Procedures: An Expert Panel Consensus

BACKGROUND One in 16 surgical patients prescribed opioids becomes a long-term user. Overprescribing opioids after surgery is common, and the lack of multidisciplinary procedure-specific guidelines contributes to the wide variation in opioid prescribing practices. We hypothesized that a single-institution, multidisciplinary expert panel can establish consensus on ideal opioid prescribing for select common surgical procedures. STUDY DESIGN We used a 3-step modified Delphi method involving a multidisciplinary expert panel of 6 relevant stakeholder groups (surgeons, pain specialists, outpatient surgical nurse practitioners, surgical residents, patients, and pharmacists) to develop consensus ranges for outpatient opioid prescribing at the time of discharge after 20 common procedures in 8 surgical specialties. Prescribing guidelines were developed for opioid-naïve adult patients without chronic pain undergoing uncomplicated procedures. The number of opioid tablets was defined using oxycodone 5 mg oral equivalents. RESULTS For all 20 surgical procedures reviewed, the minimum number of opioid tablets recommended by the panel was 0. Ibuprofen was recommended for all patients unless medically contraindicated. The maximum number of opioid tablets varied by procedure (median 12.5 tablets), with panel recommendations of 0 opioid tablets for 3 of 20 (15%) procedures, 1 to 15 opioid tablets for 11 of 20 (55%) procedures, and 16 to 20 tablets for 6 of 20 (30%) procedures. Overall, patients who had the procedures voted for lower opioid amounts than surgeons who performed them. CONCLUSIONS Procedure-specific prescribing recommendations may help provide guidance to clinicians who are currently overprescribing opioids after surgery. Multidisciplinary, patient-centered consensus guidelines for more procedures are feasible and may serve as a tool in combating the opioid crisis.

Breast reconstruction and risk of arm lymphedema development: A meta-analysis

BACKGROUND Lymphedema remains a significant complication following breast cancer surgery when there is axillary lymph node intervention. Previous systematic reviews have identified risk factors for breast cancer-related lymphedema, including increased BMI, number of lymph nodes dissected and radiotherapy. However, they have not examined the effect of breast reconstruction on lymphedema occurrence. In this systematic review and meta-analysis, we sought to evaluate the association between breast reconstruction (BR) and lymphedema. METHODS We searched PubMed (1966-2016), Embase (1966-2016), Scopus (2004-2016) and Google Scholar (2004-2016) for studies involving breast reconstruction and upper-extremity lymphedema or breast cancer-related lymphedema. Our primary outcome was lymphedema occurrence. We performed a meta-analysis using random effects due to heterogeneity of the studies. RESULTS Our search strategy identified 934 articles. After screening, 19 studies were included in our meta-analysis evaluating outcomes based on number of patients (7501) or number of breasts surgically treated (2063). Breast reconstruction was significantly associated with lower odds of lymphedema (p < 0.001) compared to mastectomy only or breast-conserving surgery. Lymphedema rates were not statistically significantly different between patients undergoing implant-based or autologous BR. CONCLUSIONS Breast reconstruction is associated with lower rates of lymphedema compared to mastectomy only or breast conserving surgery patients. Although the study does not prove causation, we hypothesize that this association is likely due to multiple factors, including a self-selecting population and mechanisms through which BR may contribute to primary or secondary prevention of lymphedema. Further prospective studies are needed to clarify this beneficial relationship between breast reconstruction and reduced lymphedema risk.

Recent Trends in Local-Regional Recurrence Rates: Implications for Therapeutic Intervention

Purpose of ReviewLocal and regional recurrences pose a significant therapeutic challenge in the field of breast cancer. Unfortunately, between 5 and 10% of patients will have this form of recurrences. This article seeks to review recent declines in locoregional recurrence risk and discuss the potential implications for the extent of therapeutic intervention currently implemented and how this may change in the future.Recent FindingsRecurrence rates have significantly decreased in recent times. Additionally, the vast amount of clinical research in the field of breast cancer allows for guidelines and traditional treatments to be updated and revamped as novel information is discovered. Patients who had neoadjuvant chemotherapy have been shown to experience a higher rate of recurrence in comparison with patients that had adjuvant chemotherapy. Radiotherapy is now recommended for patients with one to three positive lymph nodes. Axillary resections have been shown to provide no benefits to patients undergoing radiotherapy.SummaryLocal and regional recurrence rates are decreasing lately both due to improvements in various therapeutic interventions and in implementation of breast cancer screening so that cancers may be caught earlier. Due to declines in local recurrence risk, it may be reasonable to scale back surgical, chemotherapeutic, and radio-therapeutic interventions.

Tumor Site and Breast Cancer Prognosis

Introduction Various factors affect breast cancer prognosis; however, little information is available regarding the role of primary tumor site. The purpose of this study was to compare the survival and clinicopathologic characteristics of patients with breast cancer by primary tumor location. Materials and Methods We analyzed a prospectively collected single‐institution breast cancer registry. Univariate and multivariable analyses were used to evaluate the association of tumor site with positive lymph node status, presence of metastasis, time to recurrence or death, and events of recurrence or death. Patients with tumors originating from the upper‐outer quadrant were the reference group. Results From 2003 to 2015, 5295 patients with breast cancer were identified. Tumors originated from the upper‐outer quadrant (36.2%), upper‐inner quadrant (13.1%), lower‐outer quadrant (9.8%), lower‐inner quadrant (7.6%), nipple (1.2%), axillary tail (0.3%), or overlapping (24.7%). Tumors originated from overlapping lesions (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.36‐1.83) had higher odds of positive axillary lymph nodes, whereas tumors from the upper‐inner (OR, 0.68; 95% CI, 0.56‐0.84) and lower‐inner quadrant (OR, 0.72; 95% CI, 0.56‐0.93) had lower odds. Tumors from the lower‐outer quadrant were associated with lower risk of death (hazard ratio, 0.64; 95% CI, 0.46‐0.88), whereas tumors from overlapping lesions had higher risk (hazard ratio, 1.28; 95% CI, 1.05‐1.55). Conclusion The site of primary tumor may be an important characteristic affecting the prognosis of patients with breast cancer. Micro‐Abstract The present study is a retrospective review of a prospectively collected institutional cancer registry. We evaluated more than 5000 patients to explore the role of primary tumor location in breast cancer prognosis. Our results indicate that tumors of different primary tumor sites in the breast behave differently and survival differences should be expected.

Abstract 63: Enhanced Recovery After Surgery Pathway for Microsurgical Breast Reconstruction

RESULTS: The decision tree shows the associated probabilities, QALYs and costs for each clinical outcome arising from either the LVOS arm or the SSIR arm. An ICUR of