Immunotherapies in rare cancers.

Cancer remains a leading cause of death worldwide, placing a significant burden on healthcare systems as well as the global economy. Rare cancers comprise a group of about 200 cancers that individually occur at extremely low frequencies. In the United States (US), their frequency is approximately 15 cases per 100,000 people, and it is even lower in Europe with approximately 6 cases per 100,000 people. However, combined their frequency of occurrence is much higher than any singular cancer. Cancer treatment and management has tremendously improved in the last decade, particularly with the administration of immune-based therapies. The four most prevalent immune-based therapies are (1) the use of immune-checkpoint inhibitors, (2) macrophage therapy, (3) Chimeric Antigen Receptor (CAR) T cell therapy, and (4) neoantigen-based therapies. In our review, we discuss these various aproaches and their implementation in the treatment of a variety of rare cancers. Furthermore, we discuss their limitations and potential strategies to overcome them to enhance the therapeutic efficacy of these approaches. Finally, our article presents the future directions and other additional immune therapies that may be incorporated into the treatment of rare cancers.

Overall Survival Following Neoadjuvant Chemotherapy Versus Adjuvant Chemotherapy in Clinically Node Negative T1 Triple Negative Breast Cancer.

BACKGROUND: The purpose of this study was to compare the overall survival (OS) of upfront surgery followed by adjuvant chemotherapy (ACT) versus neoadjuvant chemotherapy (NACT) followed by surgery in patients with clinical T1 clinically node negative triple negative breast cancer (TNBC). PATIENTS AND METHODS: We retrospectively reviewed 48,329 women with cT1N0 TNBC from 2006 to 2016 in the National Cancer Database (NCDB). Patients were categorized into five pathologic subgroups based on ACT versus NACT and definitive pathologic stage after surgery: ACT with unchanged stage (pT0-1N0), ACT with pathologic upstage (any nodal disease, > pT1N0), NACT with pCR (ypT0-isN0), NACT with stable disease (SD) (ypT1N0), and NACT with progressive disease (PD) (any nodal disease, > ypT1N0). The primary outcome was 5 year OS. RESULTS: Patients with TNBC who underwent upfront surgery followed by ACT had better OS compared with those who received NACT (p < 0.001). The hazard ratio (HR) for death for NACT compared with ACT was 1.42 (95% CI 1.26-1.59, p < 0.001) on multivariate analysis. Patients who underwent upfront surgery followed by ACT and whose pathological stage was unchanged from clinical stage had similar outcomes compared with those who received NACT and attained pCR with 5 year OS of 92.7% versus 93.3% (p = 0.34). Patients with clinical T1cN0 tumors who underwent NACT with pCR had better outcomes compared with those who underwent ACT with unchanged stages. (p = 0.025). CONCLUSIONS: For cT1N0 TNBC patients, OS of upfront surgery followed by ACT was not inferior to those who underwent NACT. Neoadjuvant chemotherapy was associated with better outcomes in cT1c patients who attained pCR.

Clinical manifestations and expression of CD18 to guide the diagnosis of leukocyte adhesion deficiency type 1: Mexico experience.

BACKGROUND: Leukocyte adhesion deficiency type 1 (LAD-1) is an inborn error of immunity characterized by a defect in leukocyte trafficking. METHODS: Patients with clinical suspicion of LAD-1 were referred to our institution. Complete blood count and flow cytometric analysis, to identify the expression of CD18, CD11b, and the lymphocyte population phenotyping, were performed, and statistical analysis was completed. RESULTS: We report clinical manifestations and immunological findings of six Mexican patients diagnosed with LAD-1. The diagnosis was based on typical clinical presentation, combined with laboratory demonstration of leukocytosis, and significant reduction or near absence of CD18 and its associated molecules CD11a, CD11b, and CD11c on leukocytes. We found atypical manifestations, not described in other countries, such as early-onset autoimmunity or infections caused by certain microorganisms. CONCLUSIONS: Patients with LAD-1 may present with atypical manifestations, making flow cytometry an indispensable tool to confirm the diagnosis. We present the first report of LAD-1 patients in a Latin American country.

Prognostic Significance of Complete Pathologic Response Obtained with Chemotherapy Versus Chemoradiotherapy in Gastric Cancer.

BACKGROUND: Few studies have compared the survival advantage of complete pathologic response (cPR) achieved through neoadjuvant chemotherapy (nCT) versus neoadjuvant chemoradiotherapy (nCRT) in gastric adenocarcinoma. Our study utilizes a large national cancer database to address this question. PATIENTS AND METHODS: This is a retrospective review of patients with clinical stage I to III gastric adenocarcinoma from 2004 to 2013 who received nCT or nCRT. Patients who achieved cPR were selected. Associations were evaluated using Mann-Whitney U and Fisher's exact tests. Survival information was summarized using standard Kaplan-Meier methods, where estimates of the median and 5-year survival rates were estimated with 95% confidence intervals. RESULTS: A total of 413 patients who had cPR were identified. Eighty-four patients received nCT and 329 patients received nCRT. Patients in the nCRT group had higher clinical stage (88.4% vs. 75.0%) and more proximal location of tumors (95.4% vs. 45.2%). The nCT group (n = 84) had a 94% 5-year survival rate, while the nCRT group's (n = 329) rate was 60% (p < 0.001). On Cox regression modeling using a propensity-weighted approach, nCT treatment was an independent predictor of improved overall survival (nCRT vs. nCT; HR 10.44, p < 0.001). CONCLUSIONS: The use of nCT leads to a significant increase in overall survival in patients when compared with nCRT for those who achieved cPR in gastric adenocarcinoma. While this study is limited in identifying the cause for this difference in overall survival, this important finding nonetheless requires further investigation and should be considered in the development of future gastric cancer trials.

Morbidity and Outcomes After Distal Pancreatectomy for Primary Retroperitoneal Sarcoma: An Analysis by the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group.

BACKGROUND: Multi-visceral resection often is used in the treatment of retroperitoneal sarcoma (RPS). The morbidity after distal pancreatectomy for primary pancreatic cancer is well-documented, but the outcomes after distal pancreatectomy for primary RPS are not. This study aimed to evaluate morbidity and oncologic outcomes after distal pancreatectomy for primary RPS. METHODS: In this study, 26 sarcoma centers that are members of the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) retrospectively identified consecutive patients who underwent distal pancreatectomy for primary RPS from 2008 to 2017. The outcomes measured were 90-day severe complications (Clavien-Dindo ≥ 3), postoperative pancreatic fistula (POPF) rate, and oncologic outcomes. RESULTS: Between 2008 and 2017, 280 patients underwent distal pancreatectomy for primary RPS. The median tumor size was 25 cm, and the median number of organs resected, including the pancreas, was three. In 96% of the operations, R0/R1 resection was achieved. The 90-day severe complication rate was 40 %. The grades B and C POPF complication rates were respectively 19% and 5% and not associated with worse overall survival. Administration of preoperative radiation and factors to mitigate POPF did not have an impact on the risk for the development of a POPF. The RPS invaded the pancreas in 38% of the patients, and local recurrence was doubled for the patients who had a microscopic, positive pancreas margin (hazard ratio, 2.0; p = 0.042). CONCLUSION: Distal pancreatectomy for primary RPS has acceptable morbidity and oncologic outcomes and is a reasonable approach to facilitate complete tumor resection.

Outcomes of patients with invasive mucinous and tubular carcinomas of the breast.

Invasive tubular carcinoma (ITC) and invasive mucinous carcinoma (IMC) of the breast are rare histologic subtypes of breast cancer associated with favorable prognoses. The aim of our study was to investigate the outcomes for these rare subtypes using the National Cancer Database. Female patients diagnosed with ITC or IMC between 2005 and 2014 were analyzed. The primary outcome was overall survival (OS), and we analyzed its association with adjuvant therapy. 2735 patients with ITC and 5602 patients with IMC were identified. ITC presented in younger patients (57 vs. 67 years), had smaller tumors (size <1 cm, 63.1% vs. 25.4%), earlier stage, and less node-positive disease (5% vs. 8.6%), compared with IMC. Older age, government insurance, lower income, treatment in a community cancer program, large tumor size, positive nodal status, and without endocrine therapy were associated with worse OS with either subtype on multivariate analysis. No OS benefit was found for node-positive ITC that received adjuvant chemotherapy compared with those who did not. (5-year OS of 96.0% vs. 91.3%, p = 0.17).OS was improved for IMC that received adjuvant chemotherapy (10-year OS: 82.5% vs. 60.1%, p = 0.008) and endocrine therapy (10-year OS: 86.6% vs. 81.2%, p < 0.001). We concluded that ITC has favorable clinicopathological characteristics and prognosis, even with node-positive disease. ITC and IMC may need to be evaluated independently when administering adjuvant treatment plans.

Pathologic Complete Response Despite Nodal Yield Has Best Survival in Locally Advanced Rectal Cancer.

BACKGROUND: Controversy exists regarding the ability of neoadjuvant chemoradiation (nCR) to diminish lymph node yield (LNY) and how that relationship is influenced by tumor response in patients undergoing proctectomy for locally advanced rectal cancer. MATERIALS AND METHODS: The National Cancer Database was used to identify patients with rectal adenocarcinomas from 2004 to 2014. Patients that received nCR were compared with those that underwent surgery alone. LNY was stratified into <12 and ≥12 groups to determine their differences in stage specific overall survival. RESULTS: Of 56,812 patients 46.5% underwent surgery alone and 53.5% were administered nCR. There were more patients with LNY<12 in the nCR group compared to surgery alone, across all stages (44.1% versus 36.5%, P < 0.001). nCR improved OS regardless of LNY (P < 0.001). Although patients with LNY≥12 had improved overall survival, patients who had a pathologic complete response (pCR) achieved the greatest survival. In patients that did not achieve a pCR, LNY≥12 was a marker of improved OS but LNY did not impact OS in patients that attained pCR (P < 0.001). CONCLUSIONS: Although nCR diminished LNY, LNY≥12 improved OS demonstrating the importance of quality total mesorectal excision. However, LNY did not impact patients that achieved pCR. These patients, who achieved the best OS, demonstrated that tumors' biologic response to nCR had the greatest impact on patient outcomes.

Completion lymph node dissection in patients with sentinel lymph node positive cutaneous head and neck melanoma.

BACKGROUND: Relatively few cutaneous head and neck melanoma (CHNM) patients with were included in the multicenter selective lymphadenectomy trial II (MSLT-II). Our objective was to investigate whether immediate completion lymph node dissection completion of lymph node dissection (CLND) was associated with survival benefit for sentinel lymph node (SLN) positive CHNM using the National Cancer Database. METHODS: SLN positive patients with CHNM from 2012 to 2014 were retrospectively analyzed. Patients were divided into two groups: those who underwent SLN biopsy (SLNB) only versus those who underwent SLNB followed by CLND (SLNB + CLND). The primary outcome was 5-year overall survival (OS). RESULTS: Among 530 SLNB + patients, 342 patients underwent SLNB followed by CLND (SLNB + CLND). The SLNB only group had fewer positive SLN, less advanced pathologic stage, and a lower rate of adjuvant immunotherapy. There was no significant difference in 5-year OS between the two groups (51.0% vs 67%; P = .56). After adjusting for pathologic stage, there remained no difference in 5-year OS among patients with stage IIIA (63.0% vs. 73.6%, P = 0.22) or IIIB/IIIC disease (39.1% vs 57.8%; P = .52). Conclusions Using a large nationwide database, CLND was not shown to be associated with improved OS for patients with SLNB positive CHNM, validating the results of MSLT-II.

Trends in utilization of sentinel node biopsy and adjuvant radiation in women ≥ 70.

BACKGROUND AND OBJECTIVES: Omission of routine axillary staging and adjuvant radiation (XRT) in women ≥ 70 years old with early stage, hormone receptor-positive, clinically node-negative breast cancer has been endorsed based on several landmark studies. We sought to determine how much omission of axillary staging/XRT has been adopted. METHODS: Using the National Cancer Data Base, we selected malignant breast cancer cases in women ≥ 70 with ER + tumors, ≤2 cm with clinically negative lymph nodes who underwent breast conservation and had known XRT status in 2005-2015. The use of sentinel lymph node biopsy (SNB) and XRT status was summarized by year to determine trends over time. RESULTS: In total, 57 230/69 982 patients underwent SNB. Of the 12 752 patients in whom SNB was omitted, 6296 were treated at comprehensive community cancer programs. Regarding XRT, 33 891/70 114 received adjuvant XRT. There were no significant trends with regards to patients receiving SNB or those receiving XRT. CONCLUSION: Since 2005, there has been no change in SNB or XRT for early stage ER + breast tumors. However, there was a difference in omission of SNB based on facility type and setting. Future monitoring is needed to determine if these trends persist following the recently released Choosing Wisely® recommendations.

Phrenic nerve neurotization utilizing half of the spinal accessory nerve to the functional restoration of the paralyzed diaphragm in high spinal cord injury secondary to brain tumor resection.

The authors present a case of functional improvement of diaphragmatic paralysis in high spinal cord injury, performing a neurotization of the phrenic nerve with accessory spinal nerve hemisection. A C1-C2 injury of the spinal cord was diagnosed in a 12-year-old male, secondary to resection of a brainstem glioma. The patient did not have diaphragmatic motility at the moment that the mechanical ventilation was removed; however, he presented apnea. The patient underwent neurotization of the right phrenic nerve with the right spinal accessory nerve, 5 months after the injury and 6 months after nerve transfer; he had complete mobilization of the right hemidiaphragm, nevertheless persisted with paralysis of the left hemidiaphragm. This achievement reduced the use of mechanical ventilation during the day.

National Analysis of Patients With External Ear Melanoma in the United States.

BACKGROUND: External ear melanoma (EEM) is a rare condition with controversies in the literature. We analyzed patients with EEM in the United States compared to other head and neck melanomas (OHNMs). METHODS: The National Cancer Database (NCDB) was used to select patients with head and neck melanoma from January 1, 2004 to December 31, 2015. Mann-Whitney and χ tests were used to estimate statistical significance, and multivariate logistic regression to identify independent associations adjusted for confounders. RESULTS: A total of 137,233 patients met the study criteria. Among them, 16,991 (12.4%) had EEM and 120,242 (87.6%) had OHNM. For patients with EEM, the mean (standard deviation) age was 66.26 (15.798) years. Most of the patients with EEM were men (85.5%), insured by Medicare (52.4%), and treated in Academic/Research Programs (47.7%) or Comprehensive Community Cancer Programs (32.3%). Most of the EEM tumors had invasive behavior (68.0%) were Stages 0 (30.3%) or I (40.3%), and were without ulceration (76.9%). Mean time to receive any treatment was 14.1 days for EEM compared with 14.6 days for OHNM (P < 0.001). We noticed a greater proportion of EEM in men (14.8%; adjusted odds ratio [aOR] 2.72 [2.605-2.852]; P < 0.001) compared to women (6.22%; reference). EEM was an independent factor for tumor Stage I (14.47%; aOR 1.61 [1.101-1.224], P < 0.001) and invasive behavior (13.86%; aOR 1.268 [1.15-1.389]; P < 0.001) compared to OHNM. CONCLUSION: EEM was associated with higher odds of invasive behavior compared to OHNM. Furthermore, men were found to have a higher likelihood to develop EEM compared to women.

Eyelid Melanoma in the United States: A National Cancer Database Analysis.

BACKGROUND: Eyelid melanoma (EM) is a rare condition that accounts for <1% of all cutaneous melanomas. In this analysis, patients diagnosed with EM in the United States were compared to those with other melanomas in the head and neck. METHODS: The National Cancer Database was used to select patients with head and neck melanoma from 2004 to 2015. RESULTS: A total of 137,233 patients met the criteria of the study. Among them, 2694 were diagnosed with EM (2%) and 134,539 in other head and neck locations (98%). Regarding the patients with EM, the mean age was 68.56 years (standard deviation 14.04). A greater number of them were treated in Academic/Research Programs (53.6%), insured by Medicare (55.7%), tumor in situ (52.2%), stage 0 (49%), and without ulceration (75.9%). The mean time to treatment commencement was 18.96 days for EM compared to 14.4 days for other melanoma in the head and neck regions (P < 0.001). There was a greater proportion of EM in female patients (odds ratio [OR] 2.371 [2.191-2.566], P < 0.001), compared to male; age greater than 80 years (OR 1.622 [1.360-1.934], P < 0.001) compared to 0 to 49 years. Moreover, EM was an independent predictor for treatment in Academic/Research Programs (OR 1.258 [1.160-1.365], P < 0.001) and diagnosis at autopsy (OR 1.414 [1.083-1.847], P = 0.011) compared to other melanoma in the head and neck region. CONCLUSION: These novel findings have the potential to guide clinical decision making in head and neck melanoma management.

Enhanced Recovery After Surgery for Noncolorectal Surgery?: A Systematic Review and Meta-analysis of Major Abdominal Surgery.

OBJECTIVE: To evaluate the impact of enhanced recovery after surgery (ERAS) protocols across noncolorectal abdominal surgical procedures. BACKGROUND: ERAS programs have been studied extensively in colorectal surgery and adopted at many centers. Several studies testing such protocols have shown promising results in improving postoperative outcomes across various surgical procedures. However, surgeons performing major abdominal procedures have been slower to adopt these ERAS protocols. METHODS: A systematic review was performed using "enhanced recovery after surgery" or "fast track" as search terms and excluded studies of colorectal procedures. Primary endpoints for the meta-analysis include length of stay (LOS) and complication rate. Secondary endpoints were time to first flatus, readmission rate, and costs. RESULTS: A total of 39 studies (6511 patients) met inclusion and exclusion criteria. Among them 14 studies were randomized trials, and the remaining 25 studies were cohort studies. Meta-analysis showed a decrease in LOS of 2.5 days (95% confidence interval, CI: 1.8-3.2, P < 0.001) and a complication rate of 0.70 (95% CI: 0.56-0.86, P = 0.001) for patient treated in ERAS programs. There was also a significant reduction in time to first flatus of 0.8 days (95% CI: 0.4-1.1, P < 0.001) and cost reduction of $5109.10 (95% CI: $4365.80-$5852.40, P < 0.001). There was no significant increase in readmission rate (OR 1.03, 95% CI: 0.84-1.26, P = 0.80) in our analysis. CONCLUSIONS: ERAS protocols decreased length of stay and cost by not increasing complications or readmission rates. This study adds to the evidence that ERAS protocols are safe to implement and are beneficial to surgical patients and the healthcare system across multiple abdominal procedures.

Intraoperative fluid restriction in hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Multiple studies highlight the importance of liberal fluid administration in cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Over-resuscitation can delay recovery and wound healing. We report an intraoperative protocol that restricts fluid administration and minimizes morbidity. MATERIALS AND METHODS: Retrospective analysis of 35 patients that underwent CRS-HIPEC for curative intent under fluid restriction protocol from June 2015 to July 2017 was performed. Protocol consists of continuous infusion of vasopressin 0.02 units/h and maintaining urine output at 0.5 mL/kg/h via crystalloid and colloid. Endpoint was Clavien-Dindo ≥3 events within 30 d of CRS-HIPEC. RESULTS: Median age was 56 y; 71% were female. Malignancies treated: appendix (49%), colon (31%), and other (20%). Median peritoneal cancer index was 15, complete cytoreduction was achieved in 91% of patients. Median time for return of bowel function was 5 d, median length of hospital stay was 7 d. There were 28 bowel anastomoses. Median intraoperative crystalloid, colloid, and packed red blood cells were (1900, 1500, and 700 mL), respectively. Clavien-Dindo grade 3-4 events occurred in five patients. There were no deaths 30 d after surgery. CONCLUSIONS: A fluid restriction protocol appears to be safe and feasible in the setting of CRS-HIPEC for curative intent.

The first postesophagectomy chest X-ray predicts respiratory failure and the need for tracheostomy.

BACKGROUND: Esophagectomy is a major surgical procedure associated with high rates of morbidity. The purpose of this study was to determine if the immediate first postesophagectomy chest X-ray (pCXR) is associated with morbidity or mortality. METHODS: This was a single-institution analysis of patients undergoing esophagectomy, 2005-2015. A pCXR was routinely performed. A pCXR score was developed based on the number of objective abnormal findings. A statistical analysis was performed using patient/tumor variables and the pCXR score to derive adjusted odds ratios (ORs) on short-term outcomes. RESULTS: One hundred eighty-two patients had pCXRs. Scores ranged from 0 (normal) to 4 depending on the number of abnormalities, with a mean score of 1.6. The mean patient age was 60.7 y. Within the cohort, 92.9% had adenocarcinoma, 39.6% had T3/T4 tumors, and 48.4% were node positive. Open surgeries were performed in 51.6%, and 74.2% had chest anastomoses. The 30- and 90-d mortality rates were 2.2% and 3.9%, respectively. Increasing pCXR scores were associated with increased risk of prolonged intubation (OR: 1.67, 95% confidence interval [CI]: 1.21-2.36, P = 0.002) and tracheostomy (OR: 2.12, 95% CI: 1.08-4.16, P = 0.029). Multivariable analysis adjusting for age, comorbidities and performance status, histology, pathologic stage, surgical approach, and operative time confirmed a statistically significant association with the pCXR score and respiratory failure requiring tracheostomy (OR: 2.13, 95% CI: 1.03-4.39, P = 0.041). CONCLUSIONS: This is the first study to show an association between the first pCXR and respiratory failure, providing new evidence that the first pCXR has important implications for pulmonary care after esophagectomy.

Multiply recurrent retroperitoneal liposarcoma.

Retroperitoneal liposarcomas (RPLPS) are rare tumors that represent at least 50% of all retroperitoneal sarcomas. Surgical resection remains the standard of care. Unfortunately, many RPLPS patients will develop a local recurrence and subsequently die in the absence of distant metastasis. This review outlines the factors that predict local recurrence and influence the management of first and subsequent multiply recurrent RPLPS.

Laparoscopic proximal gastrectomy for gastric neoplasms.

BACKGROUND: For cancers of the distal gastroesophageal junction or the proximal stomach, proximal gastrectomy can be performed. It is associated with several perioperative benefits compared with total gastrectomy. The use of laparoscopic proximal gastrectomy (LPG) has become an increasingly popular approach for select tumors. METHODS: We describe our method of LPG, including the preoperative work-up, illustrated depictions of the key steps of the surgery, and our postoperative pathway. RESULTS: A total of 6 patients underwent LPG between July, 2013 to June, 2017. Five patients had early-stage adenocarcinoma, and 1 patient had a gastrointestinal stromal tumor. The median age of the cohort was 70, and each patient had significant comorbidities. Conversion to open was required for 1 patient. All patients had negative final margins and an adequate lymph node dissection (median number of nodes examined was 15, range 12-22). The median postoperative length of stay was 7 days (range 4-7). Two patients developed anastomotic strictures requiring intervention, and 1 patient experienced significant reflux. At a median follow-up of 11 months, there was 1 recurrence. Three patients were alive without evidence of disease, and 2 patients died from other causes. CONCLUSIONS: For carefully selected patients, LPG is a safe and reasonable alternative to total gastrectomy, which is associated with similar oncologic outcomes and low morbidity.

Does neoadjuvant/perioperative chemotherapy improve overall survival for T2N0 gastric adenocarcinoma?

BACKGROUND: The purpose of this study was to determine whether neoadjuvant and/or perioperative chemotherapy (NAC) has an overall survival (OS) benefit for patients with T2N0 gastric adenocarcinoma. STUDY DESIGN: We performed retrospective analyses using the National Cancer Data Base, 2004-2013. Patients with T2N0 gastric adenocarcinoma were divided into two treatment groups: (1) NAC plus surgery (NA + S) and (2) surgery alone (S). RESULTS: Of 1,704 patients included, 277 (16.3%) received NAC, and 1,427 (83.7%) were treated with surgery alone. Patients in the NA + S group were more likely to be younger, have fewer comorbidities, and have larger tumors located in the proximal stomach. Although in an unadjusted analysis of OS, the NA + S group had improved survival compared to the S group (HR = 0.81, 95% CI 0.67-0.99, P < 0.0001), this was not maintained in a propensity adjusted analysis (HR = 0.89, 95% CI 0.68-1.18, P = 0.42). Similarly, propensity adjusted analyses accounting for potential bias from clinical misstaging or treatment effect from NAC did not show any OS benefit from NAC. CONCLUSION: Based on the largest cohort of clinically staged T2N0 gastric adenocarcinoma, there was no OS benefit derived from NAC compared to surgery alone. For select patients with reliable preoperative staging, NAC may be omitted.

Effectiveness of Repeat 18F-Fluorodeoxyglucose Positron Emission Tomography Computerized Tomography (PET-CT) Scan in Identifying Interval Metastases for Patients with Esophageal Cancer.

INTRODUCTION: An 18F-fluorodeoxyglucose positron emission tomography-computerized tomography (PET-CT) scan is performed after neoadjuvant chemoradiation (nCRT) to restage esophageal cancer. The purpose of this study was to determine the ability of PET-CT to accurately identify interval metastatic disease following nCRT. METHODS: This was a single-institution retrospective review (January 2005-February 2012) of patients with esophageal cancer treated with nCRT who underwent pre- and post-nCRT PET-CT. RESULTS: A total of 283 patients were treated with nCRT, of whom 258 (91.2%) had both a pre- and post-nCRT PET-CT. On the post-nCRT PET-CT, 64 patients (24.8%) had interval findings concerning for metastatic disease. Of these patients, only 10 (15.6%) had true-positive findings of metastatic disease (six biopsy proven). The sites of interval metastases included bone (4), liver (3), peritoneum (1), mediastinal lymph nodes (1), and cervical lymph nodes (1). The positive predictive value of post-nCRT PET-CT for interval metastases was 15.6% (10/64), and the yield for detecting metastases since the pre-nCRT PET-CT was 3.9% (10/258). The work-up of the 54 patients (20.9% of the initial starting group) with false-positive post-nCRT findings included biopsy (24.6%) and immediate additional imaging (45.2%). A total of 208 patients proceeded with surgery: 163 (78.4%) had no new findings on post-nCRT PET-CT, and 45 (21.6%) had new false-positive findings. False-positive sites mainly included the lung (15) and liver (14). CONCLUSIONS: The yield of post-nCRT PET-CT for the detection of new metastatic disease was 3.9%. Post-nCRT PET-CT often leads to a high proportion of false positives and subsequent investigational work-up.