The Role of Surgical Resection Following Imatinib Treatment in Patients with Recurrent or Metastatic Gastrointestinal Stromal Tumors: Results of Propensity Score Analyses

Background

Although benefits of surgical resection of residual gastrointestinal stromal tumors (GISTs) after imatinib therapy have been suggested, those benefits over imatinib alone have not been proven. We compared the clinical outcomes of surgical resection of residual lesions after imatinib treatment (S group) with imatinib treatment alone (NS group) in patients with recurrent or metastatic GISTs.

Methods

A total of 134 patients (42 in the S group, 92 in the NS group) with recurrent or metastatic GIST who had stable disease for more than 6 months after responding to imatinib were included.

Results

There were no statistically significant differences in the baseline characteristics of the S and NS groups except for age and number of peritoneal metastases. The median follow-up period was 58.9 months. Progression-free survival (PFS) and overall survival (OS) were significantly longer in the S group compared with the NS group (median PFS: 87.7 vs. 42.8 months, p = 0.001; median OS: not reached vs. 88.8 months, p = 0.001). Multivariate analysis revealed that S group, female sex, KIT exon 11 mutations, and low initial tumor burden were associated with longer PFS, and S group and low initial tumor burden were associated with a longer OS. Even after applying inverse probability of treatment weighting adjustment, the S group demonstrated significantly better outcomes in terms of PFS (HR 2.326; 95 % confidence interval [CI] 1.034–5.236; p = 0.0412) and OS (HR 5.464; 95 % CI 1.460–20.408; p = 0.0117).

Conclusion

Surgical resection of residual lesions after disease control with imatinib is likely to be beneficial to patients with recurrent or metastatic GISTs.     

Patterns of Care, Prognosis, and Survival in Patients with Metastatic Gastrointestinal Stromal Tumors (GIST) Refractory to First-Line Imatinib and Second-Line Sunitinib

Background

Data regarding the management and outcome of patients with metastatic gastrointestinal stromal tumors (GIST) refractory to 1st-line imatinib and 2nd-line sunitinib are limited.

Methods

Medical records of 223 imatinib-resistant and sunitinib-resistant GIST who were treated in 11 major referral centers were reviewed.

Results

The three most frequent drugs used in the 3rd-line setting were: nilotinib n?=?67 (29.5%), sorafenib n?=?55 (24.5%), and imatinib n?=?40 (17.5%). There were 18 patients (8%) who received best supportive care (BSC) only. The median progression-free survival (PFS) and overall survival (OS) on 3rd-line treatment were 3.6?months [95% confidence interval (95% CI), 3.1?C4.1] and 9.2?months (95% CI, 7.5?C10.9), respectively. Multivariate analysis showed that, in the 3rd-line setting, albumin level and KIT/PDGFRA mutational status were significantly associated with PFS, whereas performance status and albumin level were associated with OS. After adjustment for prognostic factors, nilotinib and sorafenib provided the best PFS and OS. Rechallenge with imatinib was also associated with improved OS in comparison with BSC.

Conclusion

In the 3rd-line setting, rechallenge with imatinib provided limited clinical benefit but was superior to BSC. Sorafenib and nilotinib have significant clinical activity in imatinib-resistant and sunitinib-resistant GIST and may represent an alternative for rechallenge with imatinib.     

A multicenter phase II clinical study of oxaliplatin, folinic acid, and 5-fluorouracil combination chemotherapy as second-line treatment for advanced colorectal cancer: A Japanese experience

Purpose

This multicenter phase II study was designed to determine the efficacy and tolerability of oxaliplatin, levoforinate, and infusional 5-fluorouracil (FOLFOX4) as a second-line therapy for Japanese patients with unresectable advanced or metastatic colorectal cancer.

Methods

A total of 53 patients with progressive disease after first-line chemotherapy were enrolled in the study. The treatment was repeated every 2 weeks until disease progression or unacceptable toxicity occurred, or the patient chose to discontinue the treatment.

Results

Four patients were ineligible and one did not receive the protocol therapy. Therefore, the response rate, overall survival (OS), and progression-free survival (PFS) were evaluated in 48 patients; toxicity was evaluated in 52 patients, excluding the patient who had not received the protocol therapy. A partial response was observed in 10 patients. The overall response rate was 20.8% (95% confidence interval [CI], 10.5%?C35.0%). The median PFS was 5.6 months (95% CI, 4.1?C7.0 months) and the median OS was 19.6 months (95% CI, 11.4?C24.3 months). The most frequently encountered grade 3/4 hematological symptom was neutropenia (43.1%). The toxicity profile was generally predictable and manageable.

Conclusion

The results showed good tolerability and efficacy for second-line FOLFOX4 in patients with advanced colorectal cancer, thus indicating the promise of this regimen as an effective second-line therapy for advanced colorectal cancer in the Japanese population.     

Efficacy of fourth-line targeted therapy in patients with metastatic renal cell carcinoma: a retrospective analysis

Introduction

Evidence for sequencing targeted therapy (TT) in patients with metastatic renal cell carcinoma (mRCC) beyond third line is limited. Treatment decisions for these sequence options are largely based on individual preferences and experience. The aim of this study was to describe the efficacy and toxicity of fourth-line TT.

Materials and methods

We retrospectively reviewed patients treated with fourth-line TT for mRCC after failure of previous treatment lines at a German academic high-volume center. Out of 406 patients treated in first line, 56 patients (14.8 %) were identified with more than three lines of TT. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Cox proportional hazards models were applied to explore predictors of PFS and OS in uni- and multivariable analysis.

Results

For the fourth-line treatment, disease control rate was 35.7 %. Median OS from beginning of first-line therapy was 47.4 months (IQR 31.0–76.5). Primary resistance at first-line TT, metastatic disease at initial diagnosis and an intermediate MSKCC score were independent predictors of shorter OS from start of first-line TT. Median OS from the time of initiation of fourth-line therapy was 10.5 months (IQR 5.6–22.6). The corresponding median PFS for fourth-line TT was 3.2 months (IQR 1.6–8.0) and was not correlated with treatment response in first-line TT. The rate of toxicity-induced treatment termination was 16.1 %. Limitations are the retrospective and unicentric design with a limited number of patients.

Conclusions

Patients might benefit from subsequent treatment lines independently from treatment response in first line.

     

Prognosis After Resection of Hepatitis B Virus-Related Hepatocellular Carcinoma Originating from Non-cirrhotic Liver

Background

Long-term prognosis after resection of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) originating from non-cirrhotic liver is not fully clarified.

Methods

A total of 183 patients who underwent curative hepatectomy for HCC without cirrhosis were classified into two groups: HBV infection group (n = 124) and non-HBV infection group (n = 59). Long-term postoperative outcomes were compared between the two groups.

Results

The 5-year postoperative overall survival (OS) and disease-free survival (DFS) were 42.6 and 39.0 %, respectively, in the HBV infection group versus 52.3 and 46.5 % in the non-HBV infection group (both p > 0.05). When patients were subdivided according to TNM stages, OS in stages II or III HCC patients was similar between the two groups. In contrast, OS and DFS were significantly worse in stage I patients with HBV infection than those in stage I patients without HBV infection (p = 0.041 and 0.038, respectively). Preoperative serum HBV DNA >4 log₁₀ copies/mL and vascular invasion were independent factors associated with poor prognosis (p = 0.034 and 0.017, respectively) for patients with HBV infection.

Conclusions

After hepatic resection for HCC in non-cirrhotic liver, patients with HBV infection with early-stage tumors had worse prognosis than patients without HBV infection, possibly due to the carcinogenetic potential of viral hepatitis in the remnant liver. Antiviral therapy should be considered after hepatectomy in patients with high HBV DNA levels.     

Modern Chemotherapy Mitigates Adverse Prognostic Effect of Regional Nodal Metastases in Stage IV Colorectal Cancer

Background

In colorectal cancer, the involvement of regional lymph nodes with metastasis is an established prognostic factor. The impact of the number of positive nodes on patient outcome with stage IV disease is not well defined.

Methods

A retrospective review was performed of 1,421 patients at two tertiary referral centers with stage IV colorectal cancer who underwent primary tumor resection. Associations between regional nodes, lymph node ratio (LNR), and overall survival (OS) from date of diagnosis were analyzed.

Results

The number of positive regional nodes and LNR correlated with multiple sites of metastases (p?<?0.001). Survival was significantly associated with the number of positive nodes and LNR, with a median OS of 43 months with negative nodes, compared to 20 months with ≥7 positive nodes (p?<?0.001). The number of regional nodal metastases correlated with OS among 400 patients undergoing resection of liver metastases (p?=?0.005) but lost prognostic significance in the subset of 223 patients who underwent hepatectomy with perioperative oxaliplatin- or irinotecan-based chemotherapy (p?=?0.48).

Conclusions

In stage IV colorectal cancer, an increasing number of positive regional nodes and LNR correlate with multiple sites of metastases and poorer survival. The number of metastatic regional lymph nodes loses prognostic significance with modern chemotherapy in patients undergoing resection of liver metastases.     

Operative Microwave Ablation for Hepatocellular Carcinoma: Complications, Recurrence, and Long-Term Outcomes

Background

Treatment of hepatocellular carcinoma (HCC) in the setting of cirrhosis is limited by tumor size/location and underlying liver disease. Radiofrequency ablation is utilized in selected patients; however, local recurrence remains a concern. Microwave ablation (MWA) delivers energy to tissue in a unique fashion, reducing local recurrence. A minimally invasive operative approach allows for mobilization/protection of adjacent structures, intra-operative ultrasound, and assessment of ablation progress.

Study Design

Retrospective review of operative MWA performed for HCC in patients with cirrhosis over a 4-year period at a single center. Complications were stratified by Clavien–Dindo classification. Incomplete ablation and local, regional, and metastatic recurrence was assessed on follow-up imaging. Survival was assessed in months.

Results

Fifty-four patients with 73 tumors underwent MWA. Median tumor size was 2.6 cm (range 0.5–8.5 cm). Cirrhosis was present in 92.6 % of patients, with a Child–Pugh score of B/C in 27.8 % and hepatitis C present in 59.3 %. A minimally invasive approach was used in 94.5 % of patients. There were no deaths within 30 days. Thirty-day morbidity was 28.9 %, with grade III complications present in 11.5 %. Delayed complications occurred in 7.8 % of patients, with a 5.6 % 90-day mortality. Incomplete ablation was identified in 5.9 % of tumors with local recurrence of 2.9 % at 9 months median follow-up. Regional and metastatic recurrence occurred in 27.5 and 11.8 % at 9 months median follow-up. Median survival was not reached at 11 months median follow-up. One- and 2-year survival was 72.3 and 58.8 %.

Conclusion

Operative, preferably minimally invasive, MWA can be performed in cirrhotic patients with HCC with acceptable morbidity and low recurrence rates. High regional and metastatic recurrence rates in these patients underscore the need for minimally invasive, low morbidity approaches to liver-directed therapy.     

Unresectable Colorectal Liver Metastases: The Safety and Efficacy of Conversion Therapy Using Hepatic Arterial Infusion Immunochemotherapy with 5-Fluorouracil and Polyethylene Glycol-Interferon α-2a

Background

Hepatic arterial infusion (HAI) or systemic chemotherapy has been used to treat unresectable colorectal liver metastases. The prognosis of the disease in recent years has been improved because chemotherapy is performed before hepatectomy to reduce tumor size (conversion therapy). The purpose of this study was to investigate the safety and efficacy of conversion therapy following HAI immunochemotherapy.

Methods

Hepatic arterial infusion of 5-fluorouracil (5-FU)/polyethylene glycol (PEG)-IFNα-2a was performed in 21 patients. The primary endpoint was the safety of HAI and hepatectomy. The secondary endpoints were response rate, rate of conversion to hepatectomy, survival rate, and prognostic factors.

Results

With regard to side effects, drugs were discontinued temporarily in one patient because of a decrease in white blood cell count; however, other patients continued chemotherapy. The response rate with HAI was 61.9 %, and the conversion rate was 38.1 %. Hepatectomy was completed successfully without mortality. Median progression-free survival (PFS) was 11.5 months (with and without conversion, 16.7 and 4.8 months, respectively; p = 0.021). Median overall survival was 34.6 months (with and without conversion, 48.4 and 26.6 months, respectively; p = 0.003). Prognosis was poor when the number of metastatic tumors was ≥10 [PFS: hazard ratio (HR) 32.21, p = 0.003; overall survival (OS): HR 9.13, p = 0.07], but prognosis improved after hepatectomy (OS: HR 0.08, p = 0.09).

Conclusions

Hepatic arterial infusion immunochemotherapy with 5-FU/PEG-IFNα-2a was performed safely without major side effects. Prognosis is expected to improve after successful conversion to hepatectomy.     

Pancreastatin Predicts Survival in Neuroendocrine Tumors

Background

Serum neurokinin A, chromogranin A, serotonin, and pancreastatin reflect tumor burden in neuroendocrine tumors. We sought to determine whether their levels correlate with survival in surgically managed small bowel (SBNETs) and pancreatic neuroendocrine tumors (PNETs).

Methods

Clinical data were collected with Institutional Review Board approval for patients undergoing surgery at one center. Progression-free (PFS) and overall (OS) survival were from the time of surgery. Event times were estimated by the Kaplan–Meier method. Preoperative and postoperative laboratory values were tested for correlation with outcomes. A multivariate Cox model adjusted for confounders.

Results

Included were 98 SBNETs and 78 PNETs. Median follow-up was 3.8 years; 62 % had metastatic disease. SBNETs had lower median PFS than PNETs (2.0 vs. 5.6 years; p < 0.01). Median OS was 10.5 years for PNETs and was not reached for SBNETs. Preoperative neurokinin A did not correlate with PFS or OS. Preoperative serotonin correlated with PFS but not OS. Higher levels of preoperative chromogranin A and pancreastatin showed significant correlation with worse PFS and OS (p < 0.05). After multivariate adjustment for confounders, preoperative and postoperative pancreastatin remained independently predictive of worse PFS and OS (p < 0.05). Whether pancreastatin normalized postoperatively further discriminated outcomes. Median PFS was 1.7 years in patients with elevated preoperative pancreastatin versus 6.5 years in patients with normal levels (p < 0.001).

Conclusions

Higher pancreastatin levels are significantly associated with worse PFS and OS in SBNETs and PNETs. This effect is independent of age, primary tumor site, and presence of nodal or metastatic disease. Pancreastatin provides valuable prognostic information and identifies surgical patients at high risk of recurrence who could benefit most from novel therapies.     

Pretreatment Clinical Mediastinal Nodal Bulk and Extent do not Influence Survival in N2-Positive Stage IIIA Non-small Cell Lung Cancer Patients Treated with Trimodality Therapy

Background

Treatment for patients with N2-positive stage IIIA non-small cell lung cancer has been a controversial issue. The current study evaluated the outcomes in patients treated with trimodality therapy, which consisted of neoadjuvant radiation therapy concurrent with chemotherapy followed by surgical resection, with emphasis on clinical and pathologic nodal status.

Methods

We reviewed the records of 355 patients who were treated with trimodality therapy between 1997 and 2011.

Results

After completion of neoadjuvant chemoradiation, overall down-staging and complete response rates were 50.4 % (179 patients), and 13.2 % (47 patients), respectively. With median follow-up of 35.3 months, median times of progression-free survival (PFS) and overall survival (OS) were 16.3 months and 45.5 months, respectively. Seventeen patients (4.8 %) died of postoperative complications, and the remaining 338 patients were analyzed on prognostic factors. Old age (p = 0.032), pneumonectomy (p < 0.001), and ypN+ (p < 0.001) were found to be the significant prognosticators for worse PFS, and old age (p = 0.013), pneumonectomy (p < 0.001), and ypN+ (p < 0.001) were related to worse OS. Clinical N2 status did not influence either OS or PFS: the number of involved stations (single station vs. multi-station; p = 0.187 for PFS; p = 0.492 for OS), and bulk (clinically evident vs. microscopic; p = 0.902 for PFS; p = 0.915 for OS).

Conclusion

ypN stage was the most important prognosticator for both PFS and OS; however, neither initial bulk nor extent of cN2 disease influenced prognosis. Surgery following neoadjuvant chemoradiation should have contributed to improved clinical outcomes regardless of clinical nodal bulk and extent.     

Synchronous Resection of Primary and Liver Metastases for Neuroendocrine Tumors

Background

Surgical approach is an accepted approach for metastatic neuroendocrine tumors (NET), but the safety and effectiveness of synchronous liver metastases resection with primary and/or locally recurrent NET is unclear.

Methods

From 1992 to 2009, a total of 36 patients underwent synchronous resection of primary NET or local recurrence and liver metastases. Patients and tumor characteristics, surgical procedures, and postoperative and long-term outcome were reviewed.

Results

Primary lesions were solitary in 28 patients (80?%), with a median size of 25?mm. Liver metastases were multiple in 32 cases (89?%), with a bilobar distribution in 29 patients (81?%) and a median size of 62?mm. Resections included gastroduodenal (n?=?5), ileocolonic (n?=?18), pancreatic resection (n?=?13), and major hepatectomy (n?=?15). Resections were R0, R1, and R2 in 13, 11, and 12 cases, respectively, and tumors were classified as G1 in 20 (56?%) and G2 in 15 (42?%). There was 1 postoperative death after a Whipple/right trisectionectomy, and postoperative complication occurred in 16 patients (44?%). With a median follow-up of 56?months, 31 patients (89?%) experienced recurrence, which was confined to the liver in 90?%. Reduction of disease to liver only allowed subsequent liver-directed therapy, such as arterial embolization or percutaneous ablation, in 25 patients (71?%). Five-year symptom-free survival and overall survival were 60?%, and 69?%, respectively.

Conclusions

In highly selected patients, an initial surgical approach combining simultaneous resection of liver metastases and primary/recurrent tumors can be performed with low mortality. Most patients develop liver-confined recurrence, which is usually amenable to ablative therapies that offer ongoing disease and symptom control.     

Cardiac Angiosarcoma Management and Outcomes: 20-Year Single-institution Experience

Purpose

To identify the clinicopathologic characteristics, treatments, and outcomes of a series of patients with primary cardiac angiosarcoma (AS).

Methods

This retrospective case series was set in a tertiary referral center with a multidisciplinary clinic. Consecutive patients with institutionally confirmed pathologic diagnosis of cardiac AS from January 1990 to May 2011 were reviewed. Main outcome measures included patient demographics, tumor characteristics, management strategies, disease response, and survival.

Results

Data from 18 patients (78?% male) were reviewed. Sixteen patients (89?%) had AS originating in the right atrium. At diagnosis, eight patients (44?%) had localized/locally advanced disease and ten patients (56?%) had metastatic disease. Initial treatment strategies included resection (44?%), chemotherapy (39?%), and radiotherapy (11?%). Of the eight patients with localized/locally advanced AS, two underwent macroscopically complete resection with negative microscopic margins, one underwent macroscopically complete resection with positive microscopic margins, one underwent macroscopically incomplete resection, two received chemotherapy followed by surgery and intraoperative radiotherapy, one received chemotherapy alone, and one died before planned radiotherapy. Median follow-up was 12?months. Median overall survival (OS) was 13?months for the entire cohort; median OS was 19.5?months for those presenting with localized/locally advanced AS and 6?months for those with metastatic disease at presentation (p?=?0.08). Patients who underwent primary tumor resection had improved median OS compared with patients whose tumors remained in situ (17 vs. 5?months, p?=?0.01).

Conclusions

Cardiac AS is associated with poor prognosis. Resection of primary tumor should be attempted when feasible, as OS may be improved. Nevertheless, most patients die of disease progression.     

Long-Term Outcomes and Prognostic Factors with Reductive Hepatectomy and Sequential Percutaneous Isolated Hepatic Perfusion for Multiple Bilobar Hepatocellular Carcinoma

Background

Sorafenib is currently recommended as first-line therapy for patients with intermediate or advanced hepatocellular carcinoma (HCC) per Barcelona Clinic Liver Cancer staging. However, the median overall survival (OS) with sorafenib in these patients is 10.7 months with an overall response rate of 2 %. We retrospectively investigated the long-term outcomes and prognostic factors with reductive hepatectomy and sequential percutaneous isolated hepatic perfusion (PIHP) for refractory intermediate or advanced HCC.

Methods

A total of 68 patients who had intermediate or advanced stage HCC without extrahepatic metastases were scheduled for reductive hepatectomy plus PIHP. All patients underwent reductive hepatectomy and PIHP with mitomycin C 20–40 mg/m² and/or doxorubicin 60–120 mg/m² 1–3 months after surgery (mean, 1.51 times/patient).

Results

The objective response rate of PIHP was 70.6 % (complete plus partial response). The median OS of all 68 patients was 25 months, and the 5-year OS rate was 27.6 %. Univariate and multivariate analyses indicated that tumor response to PIHP and normalization of serum des-γ-carboxy prothrombin concentrations after PIHP were independent prognostic factors for OS.

Conclusions

The median OS of the study population treated by reductive hepatectomy and sequential PIHP was 25 months. This treatment strategy can offer a possible curative treatment to patients with refractory intermediate and advanced HCC.     

Resultados preliminares de supervivencia global y libre de progresión a tres años en una cohorte de pacientes diagnosticados de cáncer de próstata (grupo GESCAP)

Aims

To describe the 3-year progression-free survival (PFS), overall survival (OS) and disease-specific mortality in the prospective prostate cancer GESCAP cohort, as well as the progression to castration resistance in patients on hormone therapy.

Heterogeneity of Duodenal Neuroendocrine Tumors: An Italian Multi-center Experience

Background

The optimal management of duodenal neuroendocrine neoplasms (dNENs) is unclear, and endoscopic resection is increasingly performed instead of surgery.

Methods

This is a retrospective analysis of patients with histologically confirmed diagnosis of dNENs, managed at five Italian tertiary referral Centers in Italy.

Results

From 2000 to 2017, 108 patients (69 males, 39 females, median age 59.5 years) were included in this study. Seventy-one patients had G1, 21 G2, 4 G3 dNENs (12 Ki-67 not available). Fifty-four patients showed metastases at diagnosis, and 20 patients developed metachronous metastases. Thirty patients had a functioning dNEN (14 metastatic). Fifty-seven patients had the dNEN surgically resected, 16 endoscopically, 23 metastatic, received medical therapy?+?surgery or endoscopy. Seven patients underwent liver-directed therapies, and one patient had PRRT. Median OS was 187 months. During a median follow-up of 76 months, 20 patients died (19 of disease-related causes). At Cox’s multivariate proportional hazard regression, grading and age were the only variables independently related to OS. Median PFS was 170 months. Grading and staging at the initial diagnosis were independently related to PFS. No differences in terms of OS and PFS were observed between patients treated surgically or endoscopically.

Conclusions

dNENs prognosis may be highly variable. These tumors can be metastatic in up to 50% of cases at the time of first diagnosis and can develop metastases thereafter. Functioning neoplasms express high metastatic potential. Nuclear imaging should be performed to exclude distant metastases in all dNENs. Endoscopy and surgery play a primary role in the management of the disease. Further prospective studies are needed.

     

Impact of Simultaneous Diaphragm Resection During Hepatectomy for Treatment of Metastatic Colorectal Cancer

Introduction

For colorectal cancer patients with liver metastases involving the hepatic dome or invading the diaphragm, a concomitant diaphragm resection is often required to achieve negative surgical margins. The purpose of this study is to determine whether diaphragm resection during partial hepatectomy for metastatic colorectal cancer influences short-term perioperative outcomes and overall survival.

Methods

Demographics, treatments, and outcomes of 442 patients who underwent hepatic resection for metastatic colorectal cancer from 1996 to 2010 at a high-volume center were reviewed. Recurrence and survival were measured from the date of metastectomy. Actuarial curves were generated using the Kaplan?CMeier method and compared using log?Cranks testing. Multivariate predictors of worse survival were compared using a Cox-proportional hazards model.

Results

A total of 442 patients underwent hepatectomy for metastatic colorectal cancer. Of these, 34 required simultaneous diaphragm resection (DR) and 408 did not (LR). No significant differences existed in patient demographics or comorbidities. The DR group had longer median operative times (336 vs. 267?min, p?=?0.0008) but had comparable rates of perioperative morbidity and mortality. Median overall survival was shorter in the DR group compared to the LR group (18.8 vs. 36?months, p?=?0.0017). When controlling for potential cofounders, liver metastases size?>?5?cm (HR 1.45 95?% CI (1.08?C1.99), p?=?0.015) and diaphragm resection (HR?=?1.72 95?% CI (1.03?C2.86), p?=?0.038) predicted worse survival.

Conclusions

Simultaneous diaphragm resection during partial hepatectomy does not significantly influence perioperative morbidity or mortality despite longer operative times. However, patients who require diaphragm resection have less favorable survival rates as compared to those who do not.     

Diffuse Infiltrative Hepatocellular Carcinoma: Assessment of Presentation, Treatment, and Outcomes

Background

Data on infiltrating hepatocellular carcinoma (HCC) are limited. We sought to define treatment and outcome of patients treated with infiltrating HCC compared with patients who had advanced multifocal HCC.

Methods

Between January 2000 and July 2011, a total of 147 patients with advanced HCC were identified from the Johns Hopkins Hospital database (infiltrative, n?=?75; multifocal, n?=?72). Clinicopathologic data were compared by HCC subtype.

Results

Patients with infiltrating HCC had higher alfa-fetoprotein levels (median infiltrative, 326.5?ng/mL vs. multifocal, 27.0?ng/mL) and larger tumors (median size, infiltrating, 9.2?cm vs. multifocal, 5.5?cm) (P?P?=?0.001). Survival after IAT was similar among patients treated with infiltrating HCC versus multifocal HCC (hazard ratio 1.29, 95?% confidence interval 0.82?C2.03; P?=?0.27). Among infiltrating HCC patients, pretreatment bilirubin >2?mg/dL and alfa-fetoprotein >400?ng/mL were associated with worse survival after IAT (P?P?=?0.004).

Conclusions

Patients with infiltrative HCC often present without a discrete lesion on imaging. IAT for infiltrative HCC was safe and was associated with survival comparable to IAT outcomes for patients with multifocal HCC. Infiltrative HCC morphology is not a contraindication to IAT therapy in select patients.     

Downstaging in Pancreatic Cancer: A Matched Analysis of Patients Resected Following Systemic Treatment of Initially Locally Unresectable Disease

Background

Patients with locally unresectable pancreatic cancer (AJCC stage III) have a median survival of 10?C14?months. The objective of this study was to evaluate outcome of initially unresectable patients who respond to multimodality therapy and undergo resection.

Methods

Using a prospectively collected database, patients were identified who were initially unresectable because of vascular invasion and had sufficient response to nonoperative treatment to undergo resection. Overall survival (OS) was compared with a matched group of patients who were initially resectable. Case matching was performed using a previously validated pancreatic cancer nomogram.

Results

A total of 36 patients with initial stage III disease were identified who underwent resection after treatment with either systemic therapy or chemoradiation. Initial unresectability was determined by operative exploration (n?=?15, 42%) or by cross-sectional imaging (n?=?21, 58%). Resection consisted of pancreaticoduodenectomy (n?=?31, 86%), distal pancreatectomy (n?=?4, 11%), and total pancreatectomy (n?=?1, 3%). Pathology revealed T3 lesions in 26 patients (73%), node positivity in 6 patients (16%), and a negative margin in 30 patients (83%). The median OS in this series was 25?months from resection and 30?months since treatment initiation. There was no difference in OS from time of resection between the initial stage III patients and those who presented with resectable disease (P?=?.35).

Conclusions

In this study, patients who were able to undergo resection following treatment of initial stage III pancreatic cancer experienced survival similar to those who were initially resectable. Resection is indicated in this highly select group of patients.     

Current Trends in the Management of Malignant Peritoneal Mesothelioma

Background

Historically, malignant peritoneal mesothelioma (MPM) has been considered an aggressive and lethal neoplasm. However, contemporary series have demonstrated improved outcomes following a combination of cytoreductive surgery and intraperitoneal chemotherapy. We sought to assess the trends in management and survival of patients with MPM in the United States.

Methods

The Surveillance, Epidemiology, and End Results database was used to identify all patients diagnosed with malignant peritoneal mesothelioma from 1973 to 2010. Overall survival (OS) was studied with Kaplan–Meier curves and Cox regression analyses.

Results

We identified 1,591 patients with MPM. Median age at diagnosis was 64 years (IQR 53–74 years) with the majority of patients presenting with metastatic disease (n = 962, 60.5 %). A total of 980 patients (61.6 %) did not receive surgical therapy. Receipt of radical cytoreduction for patients with metastatic MPM demonstrated a significant improvement in OS compared with patients not receiving surgery (20 vs. 4 months, p < 0.01). A temporal increase was observed in OS for patients receiving surgery (1991–1995: 15 vs. 2006–2010: 38 months, p = 0.1). In multivariate models, limited (HR 0.55; 95 % CI 0.48–0.63; p < 0.01) and radical (HR 0.66; 95 % CI 0.54–0.80; p < 0.01) surgery were independently associated with improved survival.

Conclusions

In the current era, approximately three of every five patients do not receive surgery when diagnosed with MPM, although a significant survival benefit is noted in select patients. The opportunity to improve patient survival with surgical therapy is lost in a significant number of MPM patients.