Madalyn G. Neuwirth

Then and now: cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), a historical perspective

The management of peritoneal carcinomatosis, once considered a condition with few therapeutic options, has undergone dramatic change with the advancement of surgical techniques and systemic cancer therapy. Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) administration, in particular, has significantly impacted the prospect of improving outcomes for this debilitating presentation of malignancy in selected patients. This regional surgical therapy itself has undergone many stages of evolution through its original conception nearly a century ago. Progressive changes in this field have included refinements and ongoing standardization in technique, development of a common language to describe tumor burden and extent of resection, better selection of chemotherapeutics based on tumor histology, reduction of surgical morbidity and mortality, and an improved understanding of factors for appropriate patient selection, to list but a few examples. CRS/HIPEC continues to play an important role in the management of select patients with carcinomatosis of certain tumor histology and its role will no doubt continue to be redefined as new therapies emerge.

Association Between Patient Age and Lymph Node Positivity in Thin Melanoma

Importance More than half of all new melanoma diagnoses present as clinically localized T1 melanoma, yet sentinel lymph node biopsy (SLNB) is controversial in this population given the overall low yield. Guidelines for SLNB have focused on pathologic factors, but patient factors, such as age, are not routinely considered. Objectives To identify indicators of lymph node (LN) metastasis in thin melanoma in a large, generalizable data set and to evaluate the association between patient age and LN positivity. Design, Setting, and Participants A retrospective cohort study using the National Cancer Database, an oncology database representing patients from more than 1500 hospitals throughout the United States, was performed (2010-2013). Data analysis was conducted from October 1, 2016, to January 15, 2017. A total of 8772 patients with clinical stage I 0.50 to 1.0 mm thin melanoma undergoing wide excision and surgical evaluation of regional LNs were included for study. Main Outcome and Measures The primary outcome of interest was presence of melanoma in a biopsied regional LN. Clinicopathologic factors associated with LN positivity were characterized, using logistic regression. Age was categorized as younger than 40 years, 40 to 64 years, and 65 years or older for multivariable analysis. Classification tree analysis was performed to identify high-risk groups for LN positivity. Results Among the study cohort (n = 8772), 333 patients had nodal metastases, for an overall positivity rate of 3.8% (95% CI, 3.4%-4.2%). A total of 4087 (54.0%) patients were women. Median age was 56 years (interquartile range [IQR], 46-67) in patients with negative LNs and 52 years (IQR, 41-61) in those with positive LNs (P < .001). In multivariable analysis, younger age, female sex, thickness of 0.76 mm or larger, increasing Clark level, mitoses, ulceration, and lymphovascular invasion were independently associated with LN positivity. In decision tree analysis, patient age was identified as an important risk stratifier for LN metastases, after mitoses and thickness. Patients younger than 40 years with category T1b tumors 0.50 to 0.75 mm, who would generally not be recommended for SLNB, had an LN positivity rate of 5.6% (95% CI, 3.3%-8.6%); conversely, patients 65 years or older with T1b tumors 0.76 mm or larger, who would generally be recommended for SLNB, had an LN positivity rate of only 3.9% (95% CI, 2.7%-5.3%). Conclusions and Relevance Patient age is an important factor in estimating lymph node positivity in thin melanoma independent of traditional pathologic factors. Age therefore should be taken into consideration when selecting patients for nodal biopsy.

A prognostic model for resectable soft tissue and cutaneous angiosarcoma.

Angiosarcoma is an aggressive tumor rising in incidence from use of therapeutic radiation. Because of its relative rarity, prognostic factors have not been clearly delineated.

Association of First-in-Class Immune Checkpoint Inhibition and Targeted Therapy With Survival in Patients With Stage IV Melanoma

Association of First-in-Class Immune Checkpoint Inhibition and Targeted Therapy With Survival in Patients With Stage IV Melanoma The management of advanced melanoma has witnessed dramatic changes in recent years with the rational development of novel systemic therapies. The efficacies of immune checkpoint inhibitors and targeted BRAF/MEK pathway inhibitors have been demonstrated in well-designed randomized clinical trials.1-5 These drugs subsequently gained approval from the US Food and Drug Administration, first becoming available to patients with stage IV melanoma in the United States in 2011 with the approval of ipilimumab (March 2011) and vemurafenib (August 2011). The efficacies of these drugs have been demonstrated in the context of randomized clinical trials, but their association with patient outcomes on a population level is less well defined. We present here early findings of the initial national outcomes resulting from these therapies.

Trends in major upper abdominal surgery for cancer in octogenarians: Has there been a change in patient selection?

Although there is a general perception that, as the older population grows in number, more are undergoing surgery, there are few data on trends in major resections for cancer and short‐term outcomes in this group.

Predictors of false negative sentinel lymph node biopsy in trunk and extremity melanoma

Nodal recurrence following negative sentinel lymph node biopsy (SLNB) for melanoma is known as false‐negative (FN) SLNB. Risk factors for FN SLNB among patients with trunk and extremity melanoma have not been well‐defined.

Obesity is not associated with increased morbidity in patients undergoing cytoreductive surgery with intraperitoneal chemotherapy

Recent single‐institutional series have examined the relationship of body mass index (BMI) in patients undergoing cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) generally without significant increase in serious complications with increasing BMI. This study evaluates the impact of BMI on complication rates using a national cohort.

Disparities in resection of hepatic metastases in colon cancer

Background Evidence suggests that resection of synchronous hepatic metastases (SHM) in stage IV colon cancer is safe and can improve survival in select patients. Little is known, however, about the use of hepatic resection in this setting on a population level. The aim of this study was to describe trends in resection rates of SHM in patients with stage IV colon cancer using a large national cohort database. Methods A retrospective cohort study was performed of stage IV colon cancer patients during 2000-2011 in Surveillance, Epidemiology and End Results (SEER) Medicare data who had diagnosis codes confirming SHM. Univariate and multivariate logistic regression were used to identify patient factors related to receipt of hepatic resection. Results There were 11,351 patients with colon cancer and SHM. Of these patients, 465 (4.1%) underwent surgical hepatic resection. The proportion increased steadily over time from 2000-2002 (3.5%) to 2009-2011 (5.1%) (P=0.03). Patients who were older with higher comorbidity burden were less likely to undergo hepatic resection. Additionally, the odds of hepatic resection were 30% lower for African-American patients than for white patients (OR 0.70, P=0.05). Odds of hepatic resection were 44% lower for patients from ZIP Codes with >20% poverty than for patients from areas with <5% poverty (OR 0.56, P<0.001). Interestingly, among patients who underwent no surgical treatment at all, only 25% saw a surgeon after diagnosis. This number increased over time from 21.6% in 2000 to 29.1% in 2011 (P<0.001). Similar disparities noted above were seen with surgical evaluation for hepatic resection. Conclusions Despite evidence supporting the safety and efficacy of hepatic resection in the setting of SHM, few patients are seen by surgeons and go onto receive hepatic surgery. Additionally, access to hepatic resection is notably lower for African Americans and patients from areas with higher poverty rates.

The prognostic significance of tumor-infiltrating lymphocytes for primary melanoma varies by sex

Background The immune response to melanoma is manifested locally by tumor‐infiltrating lymphocytes (TILs). Men and women are known to have varying patterns of immunity, yet sex‐specific prognostic implications of TILs have not been explored. Methods Patients who had clinically localized primary melanoma with a Breslow thickness of 0.76 mm or more and underwent sentinel lymph node (SLN) biopsy at our institution were identified. The association between TILs (absent, nonbrisk, and brisk) and SLN positivity was evaluated by using logistic regression. Overall survival (OS) was evaluated by TIL status and sex. Results Among 1367 patients identified, 794 were men. TILs were brisk in 143 lesions, nonbrisk in 903, and absent in 321, which did not vary by sex (P = .71). SLN positivity was associated with TILs among men (brisk, 3.8%; nonbrisk, 16.9%; and absent, 26.6% [P < .001]). In contrast, there was no association between SLN positivity and TILs among women (P = .49). Interaction between brisk TILs and sex on SLN positivity was significant (P = .029). Among men, presence of brisk TILs was associated with prolonged OS (P = .038) but not after adjustment for SLN status (P = .42). There was no association between TIL status and OS among women. Limitations Findings from this single‐institution study have yet to be validated by other research groups. Conclusions The implications of TILs in predicting SLN positivity appear to be more relevant for men than for women.

Lymph node dissection for melanoma: where do we stand?

The extent and timing of regional lymphadenectomy and its role in patients with clinically localized primary melanoma has been the subject of considerable debate. While therapeutic lymphadenectomy for clinically positive nodes is uniformly accepted, the benefit of regional lymphadenectomy in patients with clinically uninvolved lymph nodes potentially harboring micrometastatic disease is less clear. Efforts to better select patients for complete regional lymphadenectomy after sentinel lymph node biopsy are underway. The future holds the promise of more stringent selection criteria and perhaps the identification of subgroups of patients for which a therapeutic benefit may be realized. Moreover, novel sensitive radiological techniques for detecting in vivo micrometastatic nodal disease may improve surgical precision, further decreasing potential morbidities of lymphadenectomy.