Intraperitoneal photodynamic therapy causes a capillary-leak syndrome.

BackgroundIn patients undergoing intraperitoneal (IP) photodynamic therapy (PDT), the combination of aggressive surgical debulking and light therapy causes an apparent systemic capillary-leak syndrome that necessitates significant intensive care unit (ICU) management after surgery.MethodsFrom May 1997 to May 2001, 65 patients underwent surgical debulking and PDT as part of an ongoing phase II trial for disseminated IP cancer. Perioperative data were reviewed retrospectively, and statistical analyses were performed to determine whether any identifiable factors were associated with the need for mechanical ventilation for longer than 1 day and with the occurrence of postoperative complications.ResultsForty-three women and 22 men (mean age, 49 years) were treated. Operative time averaged 9.8 hours, and mean estimated blood loss was 1450 mL. The mean crystalloid requirement for the first 48 hours after surgery was 29.3 L, and 49 patients required blood products. Twenty-four patients were intubated for longer than 24 hours, with a mean of 8.3 days for those intubated longer than 1 day. The median ICU stay was 4 days. Overall, 110 complications developed in 45 (69%) of the 65 patients. Significant complications included 6 patients with acute respiratory distress syndrome, 28 patients with infectious complications, and 4 patients with anastomotic complications. Statistical analyses revealed that surgery-related factors were significantly associated with these complication outcomes.ConclusionsPatients who undergo surgical debulking and IP PDT develop a significant capillary-leak syndrome after surgery that necessitates massive volume resuscitation, careful ICU monitoring, and, frequently, prolonged ventilatory support

Gene therapy for cancer and metastatic disease

Gene therapy has been applied to the treatment of cancer and metastatic disease for over ten years. Research in this area has utilised multiple gene therapy approaches including targeting tumour suppressor genes and oncogenes, stimulating the immune system, targeted chemotherapy, antiangiogenic strategies, and direct viral oncolysis. In recent years, gene delivery vectors have been developed that selectively target tumour cells through tumour-specific receptors, deletion of certain viral gene sequences, or incorporation of tumour-specific promoter sequences that drive gene expression. Preclinical models have produced promising results, demonstrating significant tumour regression and reduction of metastatic disease. Unfortunately, only limited responses have been observed in clinical trials. The main limitations in treating metastatic disease include poor vector transduction efficiencies and difficulties in targeting remote tumour cells with systemic vector delivery. Currently, various groups are investigating means to improve gene delivery and clinical responses by continuing to modify gene delivery vectors and by concentrating on combination gene therapy and multimodality therapy

Isolated hepatic perfusion for patients with liver metastases

Up to 80% of colorectal, melanoma, and neuroendocrine liver metastases are unresectable due to excessive tumor burden. Isolated hepatic perfusion (IHP) administers intensive therapy to the liver while limiting systemic toxicity and thus may have an important role in the management of unresectable liver metastases. This review s describes the development of IHP, initial clinical results, open and percutaneous IHP techniques, and contemporary long-term treatment outcomes. IHP with melphalan or tumor necrosis factor α (TNFα) has been shown to achieve hepatic response rates of greater than 50% with progression-free survival of greater than 12 months among patients with refractory ocular melanoma liver metastases. The only series describing outcomes of IHP for neuroendocrine liver metastases notes an overall response rate of 50% and a median actuarial overall survival of 48 months after IHP treatment with melphalan or TNFα. The majority of studies that have evaluated IHP have been performed in patients with colorectal cancer liver metastases (CRCLM). In aggregate, survival results from retrospective studies and phase I/II clinical trials suggest that IHP demonstrated no significant survival benefit compared with systemic chemotherapy alone as first-line therapy. In contrast, IHP does improve outcomes relative to that provided by second-line chemotherapy for CRCLM, with overall response rates of 60% and median duration of liver response of 12 months. Continued evaluation of IHP for unresectable liver metastases is necessary to establish its role in multidisciplinary treatment approaches

Combined Cancer Therapy: Strategies to Overcome Acquired Aromatase Inhibitor Resistance

Aromatase inhibitors (AIs) have become one of the mainstays of treatment of postmenopausal women with hormone receptor-positive breast cancer. However, acquired resistance to treatment continues to be a significant clinical challenge. There is increasing evidence from preclinical studies that activation of growth factor signaling pathways, as well as cross-talk between these pathways and estrogen receptor-alpha signaling pathways are important mechanisms that contribute to AI resistance. These preclinical studies have been the foundation for multiple randomized clinical trials that have evaluated combination targeted therapy in patients with advanced breast cancer. While the clinical benefit observed in these trials has been variable, the preclinical studies were successful in predicting clinical outcomes. This review focuses on mechanisms of acquired AI resistance and describes preclinical studies that have evaluated combination targeted therapy to overcome AI resistance, as well as clinical trials that have translated this information to the clinical setting

Handbook of breast cancer and related breast disease

Includes bibliographical references and index

Extent of regional lymph node surgery and impact on outcomes in patients with early-stage breast cancer and limited axillary disease undergoing mastectomy

Management of the axilla in patients with early-stage breast cancer (ESBC) has evolved. Recent trials support less extensive axillary surgery in patients undergoing mastectomy. We examine factors affecting regional lymph node (RLN) surgery and outcomes in patients with ESBC undergoing mastectomy. Women with clinical T1/2 N0 M0 invasive BC who underwent mastectomy with 1-2 positive nodes were selected from the National Cancer Database (2004-2015). Axillary surgery was defined by number of RLNs examined: 1-5 sentinel LN dissection (SLND), and ≥ 10 axillary LND (ALND). Binary logistic regression and survival analyses were performed to assess the association between axillary surgery and clinical characteristics, and overall survival (OS), respectively. 34,243 patients were included: 13,821 SLND (40%) and 20,422 ALND (60%). SLND significantly increased from 21% (2004) to 45% (2015) (p < .001). Independent factors associated with SLND were treatment year, non-Academic centers, geographic region, tumor histology, and postmastectomy radiotherapy (PMRT). Multivariable survival analysis showed that ALND was associated with better OS (HR 0.78, 95% CI 0.72-0.83, p < .001) relative to SLND; however, there was no difference in patients with LN micrometastases treated without RT (HR 0.87, 95% CI 0.73-1.05, p = .153) or patients receiving PMRT (HR 0.92, 95% CI 0.76-1.13, p = .433). SLND has significantly increased in patients undergoing mastectomy with limited axillary disease and is influenced by patient, tumor, and treatment factors. Survival outcomes did not differ by axillary treatment for patients with LN micrometastases treated without RT or patients who received PMRT. SLND may be considered in select patients with ESBC and limited axillary disease undergoing mastectomy

Relevance of sentinel lymph node biopsy for thick melanoma in the era of immunotherapy

Sentinel lymph node biopsy provides prognostic information in patients with thick melanoma but is often underutilized. We examine regional lymph node evaluation (RLNE) in patients with thick melanoma and the effect on treatment and overall survival (OS). Patients with clinical T4N0M0 melanoma were selected from the National Cancer Database (2004-2015). Binary logistic regression analysis was used to identify factors associated with RLNE and treatment. Overall survival analysis was performed. A total of 14 286 patients with clinical T4N0M0 melanoma were identified; RLNE was performed in 70.2% of patients, and positive LNs were identified in 27.1%. RLNE was more likely in males (OR:1.44, 95%CI: 1.32-1.56, p < .001), and patients treated at academic centers (OR:1.58, 95%CI:1.46-1.71, p < .001). Immunotherapy was more commonly used in patients with RLNE (13.9% vs 3.4%, p < .001) and was associated with positive LNs (OR:2.50, 95%CI:2.19-2.86, p < .001). The 5-year OS for RLNE was 56.9% and for no RLNE was 32.7%. Independent factors associated with better OS were treatment at an academic center (HR:0.88, 95%CI:0.84-0.93, p < .001), and immunotherapy use (HR:0.86, 95%CI:0.76-0.96, p < .001). The use of RLNE in patients with thick melanoma is important for prognosis and to risk stratify patients for selection of adjuvant therapies and clinical trials

Abstract SS1-01: Where you live matters: Impact of economic, racial/ethnic, and racialized economic residential segregation on breast cancer survival

Abstract Background:Racial and economic residential segregation remains a problem within the United States (US). Although advances in screening, detection, diagnosis, and treatment have reduced overall breast cancer mortality, well-documented socioeconomic and racial/ethnic survival disparities persist. The objective of this study was to analyze the effect of economic and racial/ethnic residential segregation as measured by the Index of Concentration at the Extremes (ICE) on breast cancer survival in South Florida. Methods:Patients treated at our medical campus with stage I-IV breast cancer from 2005-2017 were identified from our local tumor registry. Census tracts were used as neighborhood proxies. Using 5-year estimates from the American Community Survey, 5 ICE variables were computed: economic (high vs. low), race/ethnicity (non-Hispanic White (NHW) vs. non-Hispanic Black (NHB) and NHW vs. Hispanic) and racialized economic (low-income NHB vs high-income NHW and low-income Hispanics vs. high-income NHW) segregation. ICE captures spatial socioeconmic and racial/ethnic segregation by literally mapping a critical dimension of social inequality not otherwise captured by metrics that characterize areas solely in terms of the proportion of the population at a specified socioeconomic level or identified as belonging to a particular racial/ethnic group. Random effects frailty models were conducted for all patients and then stratified by race/ethnicity controlling for sociodemographics, tumor characteristics, and NCCN-guideline appropriate treatment. Results:The study population included 6,145 breast cancer patients. 52.6% were Hispanic, 26.3% were NHW, and 17.2% were NHB. After controlling for multiple covariates, those living in extreme economically disadvantaged neighborhoods had a statistically significant increased mortality compared to those living in more economically advantaged neighborhoods (HR: 1.58 95%CI: 1.29, 1.92, p<0.001), Table 1. Patients living in an economically disadvantaged NHB neighborhood also had a statistically significant increased mortality compared to those living in more economically advantaged NHW neighborhoods (HR: 2.0 95% CI: 1.54, 2.60, p<0.001). In race-stratified analyses, an NHW person living in a predominantly economically disadvantaged NHB neighborhood had increased mortality compared to a NHW person living in an economically advantaged NHW neighborhood (HR: 2.02 95%CI: 1.19-3.41, p< 0.0071) controlling for tumor subtype and NCCN-guideline appropriate treatment. Conclusion:This is the first study to evaluate breast cancer survival by ICE, which identifies inequitable associations by conveying extreme concentrations of both economic deprivation/privilege and racial/ethnic segregation. Our study suggests that breast cancer survival disparities is partly influenced by extreme racial/ethnic and economic segregation. Even when accounting for sociodemographics, tumor characteristics, and NCCN-guideline appropriate treatment, survival disparities remained, suggesting potential social and environmental factors impacting survival. To address these disparities, effective interventions are needed that account for the social and environmental contexts in which cancer patients live and are treated. Table 1: Breast Cancer Hazard Ratio by Economic, Racial/Ethnic, and Racialized Economic Residential Segregation Residential SegregationType of Segregation (ICE)QuartileModel 1Model 2Model3HR (95% CI)HR (95% CI)HR (95% CI)Economic SegregationQ11.83 (1.1, 3.03)*1.64 (0.89, 3.02)1.58 (1.29, 1.92)*Economic SegregationQ22.36 (1.48, 3.76)*2.45 (1.38, 4.34)*1.44 (1.16, 1.79)*Economic SegregationQ31.16 (0.72, 1.8)1.08 (0.61, 1.9)1.16 (0.94, 1.44)Economic SegregationQ4111NHB SegregationQ11.6 (0.9, 2.84)1.42 (0.72, 2.82)1.41 (0.96, 2.07)NHB SegregationQ20.92 (0.52, 1.6)0.91 (0.47, 1.77)1 (0.68, 1.48)NHB SegregationQ30.61 (0.29, 1.26)0.85 (0.37, 1.94)0.82 (0.52, 1.31)NHB SegregationQ4111Hispanic SegregationQ11.38 (0.83, 2.28)1.13 (0.61, 2.08)1.36 (1.12, 1.66)*Hispanic SegregationQ279 (0.47, 1.32)0.74 (0.4, 1.38)0.86 (0.67, 1.08)Hispanic SegregationQ30.94 (0.59, 1.49)0.98 (0.57, 1.67)1.05 (0.86, 1.29)Hispanic SegregationQ4111NHB Economic SegregationQ12.68 (1.6, 4.47)*2.02 (1.09, 3.74)2 (1.54, 2.6)*NHB Economic SegregationQ21.85 (1.15, 2.97)*1.39 (0.79, 2.44)1.56 (1.22, 2.02)*NHB Economic SegregationQ31.2 (0.69, 2.07)1.09 (0.58, 2.06)1.19 (0.88, 1.6)NHB Economic SegregationQ4111Hispanic Economic SegregationQ11.91 (1.19, 3.07)*1.45 (0.83, 2.54)1.64 (1.24, 2.15)*Hispanic Economic SegregationQ21.45 (0.8, 2.62)1.06 (0.52, 2.17)1.44 (1.06, 1.96)*Hispanic Economic SegregationQ31.26 (1.73, 2.18)0.95 (0.49, 1.84)1.11 (0.8, 1.54)Hispanic Economic SegregationQ4111Model 1: Adjusted for ICE, race/ethnicity, age, insuranceModel 2: Adjusted for Model 1 covariates plus receptor status, clinical stageModel 3: Adjusted for Model 1 and 2 covariates plus stage appropriate treatmentQ1: Most disadvantaged neighborhoods; Q4: Reference: most advantaged neighborhoods.*p < 0.05 Citation Format: Neha Goel, Kristin N Kelly, Sina Yadegarynia, Seraphina Choi, Susan B Kesmodel, Ashly Westrick. Where you live matters: Impact of economic, racial/ethnic, and racialized economic residential segregation on breast cancer survival [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SS1-01