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BACKGROUND/AIM Computed tomography and positron emission tomography cannot detect all minute distant metastases and fully evaluate extensive vascular invasion in patients with pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate predictors of laparotomy only and palliative surgery in PDAC patients planning surgical resection. PATIENTS AND METHODS We reviewed 239 PDAC patients planning surgical resection. Patients were divided into two groups based on resection status. Multivariate analyses were performed to identify predictors of unresectable disease at laparotomy. RESULTS Twenty-five patients had unresectable disease at laparotomy. Multivariate analysis revealed that anatomical borderline resectable status (yes/no) (HR=5.458, p=0.012), pretreatment CA19-9 (>260/≤260 ng/ml) (HR=4.907, p=0.041), and tumor size (>25/≤25 mm) (HR=21.42, p=0.004) were associated with unresectable disease at laparotomy. CONCLUSION Borderline resectable status, pretreatment CA19-9, and tumor size were closely associated with unresectable disease at laparotomy in PDAC patients planning surgical resection.

Introduction: Malignant pleural mesothelioma (MPM) has limited treatment options with minimal new therapy approvals for unresectable disease in the past 15 years. However, considerable work has occ...

There is a lack of clear guidelines on optimal radiotherapy dose regimen for elderly breast cancer patients. This review summarizes the current evidence on role of hypofractionated radiotherapy in elderly breast cancer. Also, suggestions have been provided on the best fractionation approaches based on current evidence. Hypofractionated radiotherapy is feasible and well tolerated in elderly breast cancer patients with both early and locally advanced disease. Ultra-hypofractionated regimen seem appropriate for palliation of unresectable primary breast disease and could become a safe approach for adjuvant treatments. Hypofractionated radiotherapy should be considered for treatment of elderly breast cancer for curative intent, as well as for palliation.

Intrahepatic cholangiocarcinoma is the second most common primary hepatic malignancy and poses a therapeutic challenge owing to its late-stage presentation and treatment-resistant outcomes. Most patients are diagnosed with locally advanced, unresectable disease and are treated with a combination of systemic and local regional therapies. Transarterial radioembolization offers a survival benefit and a favorable side effect profile, with a growing body of evidence to support its use. Herein, we review patient selection and detail outcomes of radioembolization for intrahepatic cholangiocarcinoma, together with mention of competing treatments.

Colorectal cancer (CRC) is a commonly diagnosed malignancy. The prognosis of patients with unresectable, metastatic colorectal cancer (mCRC) is dismal and medical treatment is mainly palliative in nature. Although chemotherapy remains the backbone of treatment, the landscape is changing with the understanding of its heterogeneity and molecular biology. First-line therapy relies on a combination of chemotherapy and targeted therapies, according to clinical patient characteristics and tumor molecular profile. Here we review current evidence from randomized clinical trials for using chemotherapy doublets or triplets, and for the addition of bevacizumab or anti-epidermal growth factor receptor (EGFR) agents. Novel therapies developed for small, selected populations are also discussed.

Adenoid cystic carcinoma is a rare disease and characterised by slow but unrelenting local progression and risk of haematogenous metastases. We present a case of locally unresectable disease where PSMA PET/CT provided complementary staging and early treatment response assessment.

Hepatocellular carcinoma is a leading cause of cancer death worldwide. Chemoembolization is the mainstay of therapy for unresectable disease, and also serves as a bridge to transplantation. This chapter reviews patient selection, periprocedural care, and technical requirements for safe and effective performance.

Introduction Hepatic arterial infusion pump (HAIP) therapy for colorectal liver metastases (CRLM) is beneficial in selected patients yet wide acceptance in the oncology community is lacking. Methods A surgeon-led team implemented a HAIP program in 2012. Pumps were placed by laparotomy for CRLM and fluorodeoxyuridine was infused via HAIP every 28 days without systemic chemotherapy supervised by the operating surgeon. Results Sixty patients were treated with HAIP, either in the adjuvant setting after liver resection or ablation of CRLM in 26 (43%) patients or with the unresectable disease in 34 (57%). Perioperative complications occurred in 19 (32%) and pump-specific complications in 14 (23%) that included intrahepatic biliary stricture in one (2%). Time to liver progression was a median 9.2 months (95% CI, 3.1-15.3 months) in unresectable patients and liver recurrence was a median 24.7 months (2.5-46.9 months) in the adjuvant group. Estimated 3-year overall survival from the time of HAIP placement was 64% in the adjuvant group and 37% in the unresectable group. Sarcopenia was prevalent (48%) and was associated with a worse survival (HR 2.4, 95% CI, 1.1-5.0). Conclusion A surgeon-led HAIP program may achieve outcomes on par with those of experienced centers and foster strong relationships between surgical and medical oncologists.

Immune checkpoint inhibitors and BRAF-MEK inhibitors have revolutionized the management and prognosis of patients with metastatic melanoma. However, there is minimal evidence to guide their incorporation into current treatment paradigms for unresectable stage III disease. The era of effective systemic therapies has prompted a discussion about what constitutes unresectable disease. Patients with unresectable stage III disease can experience significant morbidity from their disease and locoregional therapies, and may progress with distant metastases. Despite increasing use of systemic therapies in unresectable stage III disease, further evidence is needed to establish their degree of benefit in this population.

Aim of the study Recent advances in chemotherapy have increasingly enabled conversion surgery (CS) in patients with initially unresectable pancreatic cancer (PC), but patient selection remains controversial. We examined the characteristics of patients who would benefit from this procedure. Material and methods The clinical and pathological data of 38 patients with unresectable PC, who underwent CS after a favourable response to chemo(radio)therapy at our institute, were investigated. Univariate and multivariate analyses were performed to identify predictors for overall survival (OS). Several inflammation-based scores, such as the modified Glasgow prognostic score (mGPS), were also evaluated. Results The patients included 13 with locally advanced disease and 25 with metastatic disease. After non-surgical treatment with a median duration of six months, 27 patients (71%) underwent R0/1 resection, and the remainder underwent R2 resection. The two-year and five-year OS from the initial treatment for all patients were 64% and 29%, respectively, and the median survival was 29.1 months. Univariate analysis showed that age < 62 years, preoperative CA19-9 decrease rate ≥ 89%, preoperative mGPS-0, and R0/1 resection were related to a favourable OS. R0/1 resection and mGPS-0 were independent prognostic factors according to multivariate analysis. Conclusions Preoperative mGPS is a potential predictor of survival and can aid selection of patients for whom CS could yield promising prognosis for initially unresectable PC.

Objectives: Our study evaluates survival of women with early-stage ovarian cancer treated with neoadjuvant chemotherapy (NAC) vs primary debulking surgery (PDS). Methods: We used the 2004-2015 NCDB to identify women with early ovarian cancer treated with multiagent chemotherapy and appropriate surgery. Logistic regression was used to identify predictors of NAC. Overall survival estimates were compared using Kaplan-Meier analysis and Cox proportional hazards regression models were used to examine variables. Results: In total, 14,627 women were included. The majority (96%) underwent PDS while (4%) underwent NAC. Median survival times were 40 months (95% CI [37.190-47.280], P Download : Download high-res image (124KB) Download : Download full-size image Conclusions: Women treated with neoadjuvant chemotherapy (NAC) had worse overall and 5-year survival. This finding agrees with the accepted convention of reserving NAC for women with advanced, unresectable disease.

e16217 Background: The vast majority of pancreatic ductal adenocarcinoma (PDAC) patients have unresectable disease at diagnosis, with only about 20% presenting with either resectable or borderline resectable tumors and who may receive adjuvant with or without neo-adjuvant treatment with surgery. This study seeks to characterize these treatment patterns in the real-world setting. Methods: This was a retrospective observational study to evaluate adjuvant treatment of PDAC patients, with or without neo-adjuvant treatment in the U.S. Patients with at least two medical claims with a primary diagnosis for PDAC between 2016 to 2019 were identified in the Truven MarketScan administrative claims database. A surgical resection within 3 months of any primary PDAC coded medical encounter was the index event, with patients required to be continuously enrolled for at least 3 months before and 6 months after the surgery. Patient demographics and treatment patterns (chemotherapy, radiotherapy, and chemoradiation) were evaluated over the pre-index (3 months) and post-index (3 and 6 months) observation windows. Neo-adjuvant and adjuvant treatment patterns were reported for the overall population and also stratified by age and sex. Results: 737 patients met the selection criteria with a majority (n=520, 71%) being

Introduction: Pancreatic cancer is a leading cause of cancer-related death. Its diagnosis is often delayed and patients are frequently found to have unresectable disease. Patients diagnosed with new-onset diabetes have an 8-fold risk of harboring pancreatic cancer. Adrenomedullin has been claimed to mediate diabetes in pancreatic cancer. New screening tools are needed to develop an early diagnosis protocol. Methods: Patients aged 45-75 years within 2 years of first fulfilling the ADA criteria for diabetes will be prospectively enrolled in this study. Sepsis, renal failure, microangiopathy, pregnancy, acute heart failure and previous malignancies will be considered as exclusion criteria. Results: 440 patients diagnosed with new-onset diabetes will be enrolled and divided into 2 groups: one with high adrenomedullin levels and one with low adrenomedullin levels. Patients will undergo 3 years’ follow-up to detect pancreatic cancer development. Conclusions: Identifying a marker for pancreatic cancer among high-risk patients such as new-onset diabetics might lead to the identification of a subpopulation needing to be screened in order to enable early diagnosis and treatment of a highly lethal tumor. Trial registration: This trial was registered at ClinicalTrials.gov on May 25, 2015 under registration number NCT02456051.

Introduction: The liver is the most common metastatic site in colorectal cancer with more than half the patients developing a liver metastasis either at the time of their diagnosis (synchronous) or later (metachronous). Surgical resection remains the principal curative approach that offers significant survival improvements. However, upfront surgery is only possible in about 10-20% of patients at the time of diagnosis, making the consideration of other treatment modalities essential. Areas covered: In this review, the authors provide an overview of the standard approaches for the initial management of patients with colorectal cancer with liver metastases. They then provide an up-to-date discussion of first-line systemic chemotherapy/targeted therapy options in the contexts of initially resectable and unresectable disease and review toxicities and complications following these options. Expert opinion: Advances in chemotherapeutic agents and biological targeted therapies have improved the prognosis of colorectal cancer with liver metastases. However, there is still no 'single best approach', making further trials necessary to provide more evidence.

Immunotherapy has revolutionized the treatment of melanoma, with implications for the surgical management of this disease. Surgeons must be aware of the impact of various immunotherapies on patients with resectable and unresectable disease, and how surgical decision-making should progress as a result. We expect that current and developing immunotherapies will increase surgeon involvement for resection of metastatic melanoma, whether for tumor harvests to generate autologous lymphocytes or for consolidating control of disease beyond what immunotherapies alone can achieve. Despite remarkable advancements in the field, significant work is needed to optimize the immuno-modulation that targets cancers while minimizing toxicity for patients.

284 Background: Esophagogastric cancer (EGC) carries a heavy mortality burden owing largely to high rates of unresectable disease at diagnosis. Among patients not undergoing curative-intent therapy, access to care may vary. We examined the geographic distribution of care delivery and survival across a jurisdiction, and its relationship with distance to cancer centres (CCs), for non-curative EGC. Methods: We conducted a population-based analysis of adults with non-curative EGC from 2005-2017 using linked administrative healthcare datasets in Ontario, Canada. Outcomes were medical oncology consultation, receipt of chemotherapy, and overall survival (OS). We used geographic information system analysis to map locations of CCs and outcomes across census divisions. Regions of discordance between care use and OS were identified with bivariate choropleth maps. Multivariable modified Poisson models assessed the relationship between distance to the nearest CC and outcomes, adjusting for demographic, clinical, and socioeconomic factors. Results: Of 10,228 patients surviving a median of 5.1 months (IQR: 2.0-12.0), 68.6% had medical oncology consultation and 32.2% received chemotherapy. Regions of comparable OS and care delivery were clustered throughout the province. CCs were distributed unevenly, with higher levels in Southern Ontario. Higher-level CCs clustered in regions with higher rates of consultation, chemotherapy use, and OS. Each increment in distance from location of residence to the nearest CC (11-50, 51-100, and ≥101 km) was associated with lower likelihood of seeing medical oncology and receiving chemotherapy, and inferior OS, compared to ≤10 km. Conclusions: A third of patients with non-curative EGC did not see medical oncology, and the majority did not receive chemotherapy. Care delivery and OS exhibited high geographic variability. Location of residence influenced access to care and OS, with inferior outcomes for those living further from a CC. These findings are important for designing interventions and policies to reduce disparities in access to care and outcomes for non-curative EGC.

690 Background: Downstaging of pancreatic adenocarcinoma in patients presenting with nonmetastatic, unresectable disease has proven to be associated with improved clinical outcomes. Efforts at rescuing these patients to become surgical candidates are commonly attempted with a combination of systemic and radiation strategies. In this study, we aimed to determine tumor downsizing in patients that underwent neoadjuvant systemic therapy followed by a curative-intended surgical resection. Methods: A retrospective review of consecutive patients that underwent surgical resection for pancreatic adenocarcinoma following a course of neoadjuvant therapy was performed. Basic demographics, endoscopic ultrasound (EUS) findings, chemotherapy regimens and duration, rates of radiotherapy, type of surgical procedure and pathologic results were recorded. Tumor response to neoadjuvant therapy was established by correlating EUS- to pathologic tumor dimensions. Analysis of the data was done using Mann-Whitney U test, Pearson correlation and Chi-square when indicated. Results: A total of 97 patients were analyzed; 40 underwent neoadjuvant chemotherapy (13 patients also received concurrent radiation therapy). In those 57 patients that were resected upfront, EUS tended to underestimate tumor sizes significantly compared to pathologic dimensions, with an average difference between dimensions of 0.66 cm (p = 0.0004). Within the group treated with neoadjuvant chemotherapy, 90% of patients had downsizing at an average of 8% of tumor size. There were no differences in rates of tumor downsizing between FOLFIRINOX or Gemcitabine/Nac-paclitaxel treated patients. In addition, there were no correlations in margin status (R0) based on chemotherapy used, with both regimens achieving a similar rate of R0 resections (mean 61%). The type of chemotherapy regimen used did not affect the ratio of positive lymph nodes harvested. Conclusions: In patients that present with borderline resectable pancreatic adenocarcinoma, a course of neoadjuvant therapy results in tumor downsizing in a significant number allowing for margin negative resections. These results were seen regardless of the chemotherapeutic regimens utilized.

The aim was to evaluate the outcome of treatment-naive patients with synchronous metastatic rectal cancer after chemotherapy with FOLFOXIRI followed by local therapeutic procedures of all tumor lesions as complete as possible. We reviewed data of 30 patients with synchronous distant metastatic rectal cancer who underwent chemotherapy with FOLFOXIRI and subsequent local therapy in our institution. Median follow-up was 28 months (range: 8; 74). Cumulative overall survival (OS) and progression-free survival (PFS) was 93.3, 76.9, 55.6% and 46.2, 29.7, 29.7% after 1, 2, 4 years. Non-response to chemotherapy with FOLFOXIRI was associated with a highly significant decreased OS (p

In-transit melanoma is an uncommon pattern of recurrence, but presents unique management challenges and opportunities for treatment. The clinical presentation usually involves from 1 to more than 100 small subcutaneous or cutaneous nodules, ranging from submillimeter to multiple centimeters in diameter. Regional chemotherapy techniques are a mainstay of treatment of patients without systemic disease spread. Future applications of regional therapy are likely to involve combination therapy with cytotoxic agents and novel immune modulators. Regional therapy provides distinct opportunities for the treatment of unresectable disease, and offers a unique platform for investigation of novel therapeutics in early-stage clinical trials.

When it comes to cancer treatment, few have been as difficult as renal cell carcinoma (RCC). Many patients present with advanced or unresectable disease, and up to 30% of patients who have initiall...

Background and study aims It is unclear to what extent EUS influences the surgical management of patients with pancreatic adenocarcinoma. This systematic review sought to determine if EUS evaluation improves the identification of unresectable disease among adults with pancreatic adenocarcinoma. Patients and methods We searched MEDLINE, EMBASE, bibliographies of included articles and conference proceedings for studies reporting original data regarding surgical management and/or survival among patients with pancreatic adenocarcinoma, from inception to January 7th 2017. Our main outcome was the incremental benefit of EUS for the identification of unresectable disease (IBEUS). The pooled IBEUS were calculated using random effects models. Heterogeneity was explored using stratified meta-analysis and meta-regression. Results Among 4,903 citations identified, we included 8 cohort studies (study periods from 1992 to 2007) that examined the identification of unresectable disease (n = 795). Random effects meta-analysis suggested that EUS alone identified unresectable disease in 19% of patients (95% confidence interval [CI], 10-33%). Among those studies that considered portal or mesenteric vein invasion as potentially resectable, EUS alone was able to identify unresectable disease in 14% of patients (95% CI 8-24%) after a CT scan was performed. Limitations The majority of the included studies were retrospective. Conclusions EUS evaluation is associated with increased identification of unresectable disease among adults with pancreatic adenocarcinoma.

Background This study investigates whether there has been any survival improvement for hepatocellular carcinoma patients with resectable and unresectable lung metastases over time. Methods The data of 280 hepatocellular carcinoma patients who developed metachronous lung metastases after hepatectomy with curative intent were analysed. Overall survival was compared in patients with resectable and unresectable lung metastases and in different periods (Era I: 1989–1995, Era II: 1996–2010). Results The median overall survival of patients with unresectable and resectable diseases was 7.46 and 40.36 months, respectively (P < 0.0001). In Era I, the median overall survival of patients with unresectable and resectable diseases was 5.59 and 43.15 months, respectively (P < 0.0001). The corresponding figures in Era II were 8.38 and 32.90 months (P < 0.0001). The overall survival of patients with resectable disease did not differ significantly in the two eras but there was a significant improvement in survival of patients with unresectable disease in Era II. Their 1-year, 3-year and 5-year survival rates in Era I versus Era II were 11.1% versus 38.4%, 5.6% versus 9.1% and 2.8% versus 3.5%, respectively (P = 0.041). The corresponding figures for their counterparts in the resectable group were 90% versus 85.8%, 80% versus 45.9% and 40% versus 29.5%, respectively (P = 0.443). Conclusions Patients with resectable lung metastases had better overall survival than those with unresectable lung metastases. Notably, patients with unresectable lung metastases had significant improvement in survival over the years.

413 Background: Fibrolamellar carcinoma (FLC) is a very rare liver tumor, comprising only 1% of all primary liver tumors in the United Sates. There is no standard of care for unresectable disease. Current practices are based on small retrospective studies and case series. We aim to analyze the clinicopathologic factors and treatment modalities affecting overall survival (OS) in FLC. Methods: Using the National Cancer Data Base (NCDB), we identified 496 patients diagnosed with FLC between 2004 and 2015. Simple descriptive statistics were created for all covariates. Survival data was available on 461 patients. Kaplan Meier Survival analysis was used for unadjusted results, and Cox proportional hazards model was used for multivariable analysis. The objective of the study is to identify predictors of survival in FLC. Results: The median age at diagnosis was 32 (range 18-90) years. Fifty-six percent were males. Stage distribution included 114 (31.2%), 43 (11.8%), 89 (24.3%) and 120 (32.8%) patients for stages I, II, III and IV, respectively. Median follow-up was 24 months. Surgery of the primary site was performed on 282 (56.9%) of patients, 146 (51.2%) of which had regional lymph node dissection. Seventy (47.9%) patients had pN+ disease. Among patients with available serum alpha fetoprotein (AFP) data, 146 (42.5%) had abnormal AFP levels (> 20 ng/mL). Median OS by stage were 78.5, 87.2, 18.6, and 10.6 months for stages I, II, III, and IV, respectively. Multivariate analysis showed that age (HR 1.01, p < 0.0001), pN+ (HR 2.31, p = 0.0003), and abnormal AFP (HR 1.69, p = 0.0003) were negative predictors of survival. Among metastatic patients, 57 (11.4%) had metastatectomy. Metastatectomy improved overall survival in stage IV FLC, HR 0.51 (95% CI 0.29-0.89). Conclusions: Independent predictors of decreased OS in patients with FLC include age, pN+ and abnormal AFP. Metastatectomy improved OS. FLC is a rare disease entity that warrants further investigations to better delineate optimal treatment approaches.

In 2017, results from phase III trials demonstrated the impressive safety and efficacy of adjuvant targeted and immune therapies in patients with resectable stage III–IV melanoma, and raised questions about the surgical management of patients with microscopic sentinel-lymph-node metastases. For patients with unresectable disease, new overall survival data added to the debate about the relative benefits of single-agent anti-PD-1 versus combined anti-PD-1 and anti-CTLA-4 immunotherapy.

Immunotherapies and BRAF and MEK inhibitors have dramatically improved outcomes in advanced melanoma. The availability of these novel approaches has necessitated changes to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). The NCCN Guidelines feature algorithms that aid clinicians in selecting initial therapy, which now includes anti-programmed death protein receptor-1 PD-1 inhibitors among the recommended systemic therapy options for patients with metastatic or unresectable disease.

The surgical palliation of pancreatic cancer remains an important component of the treatment of this disease. The introduction of a new aggressive and effective chemotherapy regimen (FOLFIRINOX), interdisciplinary palliative care, and minimally invasive approaches for providing palliation are all factors that expand the role of the surgeon in the care of patients with unresectable disease. Currently, the role of the surgeon in the palliation of pancreatic cancer is (1) to identify patients with incurable disease (either preoperatively or intraoperatively), (2) to determine the optimal palliative technique to optimize results and preserve resources, and (3) to perform palliation of symptoms with low morbidity and mortality. The 3 most common symptoms of pancreatic cancer requiring surgical palliation are obstructive jaundice, gastric outlet obstruction, and tumor-associated pain. It is important that the surgeon recognizes the full range of surgical and nonoperative techniques available and contributes to the decision making as to the most appropriate method for each individual patient.

In the last module of this consensus, controversial topics were discussed. Management of the disease after progression during first line chemotherapy was the first discussion. Next, the benefits of liver resection in the presence of extra-hepatic disease were debated, as soon as, the best sequence of treatment. Conversion chemotherapy in the presence of unresectable liver disease was also discussed in this module. Lastly, the approach to the unresectable disease was also discussed, focusing in the best chemotherapy regimens and hole of chemo-embolization. RESUMO Neste último módulo do consenso, abordou-se alguns temas controversos. O primeiro tópico discutido foi o manejo da doença após progressão na primeira linha de quimioterapia, com foco em se ainda haveria indicação cirúrgica neste cenário. A seguir, o painel debruçou-se sobre as situações de ressecção da doença hepática na presença de doença extra-hepática, assim como, qual a melhor sequência de tratamento. O tratamento de conversão para doença inicialmente irressecável também foi abordado neste módulo, incluindo as importantes definições de quando se pode esperar que a doença se torne ressecável e quais esquemas terapêuticos seriam mais efetivos à luz dos conhecimentos atuais sobre a biologia tumoral e taxas de resposta objetiva. Por último, o tratamento da doença não passível de ressecção foi discutida, focando-se nos melhores esquemas a serem empregados e seu sequenciamento, bem como o papel da quimioembolização no manejo destes pacientes.

Adjuvant therapy employing cytotoxic chemotherapy, molecularly targeted agents, immunologic, and hormonal agents has shown a significant impact upon a variety of solid tumors. The principles that guide adjuvant therapy differ among various tumor types and specific modalities, but generally indicate a greater impact of therapy in the postsurgical setting of micrometastatic disease, for which adjuvant therapy is commonly pursued, vs. the setting of gross unresectable disease. This review of adjuvant therapies in current use for five major solid tumors highlights the rationale for current effective adjuvant therapy, and draws comparisons between the adjuvant regimens that have found application in solid tumors.

Thermoablation is a local therapy that is effective in in situ destruction of colorectal liver metastasis while preserving surrounding normal liver tissue. It is less invasive compared to surgery, easy to use, and can be repeated. The therapy provides local control of unresectable disease and is an alternative therapy for small resectable lesions in patients with insufficient hepatic reserve after resection or coexistent comorbid conditions. It can artificially increase the resection margin thus increasing the number of patient candidate for resection. When used in conjunction with liver resection it clears the liver of multiple lesions that are surgically inaccessible or unresectable. Main limitations of the treatment are local recurrence of the disease, treatment-related complications, and questionable impact on patient. Outcome of therapy can be improved when used as part of multimodality treatment. J. Surg. Oncol. 2010; 101:699-705. © 2010 Wiley-Liss, Inc.

Giant cell tumour of bone (GCT) is the most common benign bone tumour and afflicts a young population. Treatment options for patients with unresectable disease have remained fairly static for the past three decades.Recent discoveries have identified a key role for the osteoclast differentiation factor, receptor activator of nuclear factor kappa B (NF-kappaB) ligand (RANKL), in the genesis of GCT. The development of the fully human monoclonal antibody to RANKL, denosumab, has led to a clinical trial in unresectable GCT. This study demonstrated an 86% response rate, with comparable evidence of clinical benefit, and was well tolerated. Other pathways that may present targets for therapy include the hypoxia-angiogenesis axis and the colony stimulating factor 1 receptor.Denosumab presents a new treatment option for patients with previously untreatable GCT. The eventual role of denosumab and other targeted agents in the treatment of GCT and related disorders is currently the subject of active study.

“Cure” for patients with stage IV colorectal cancer remains elusive, but for a growing subset of patients with colorectal liver metastases (CLMs), cure (ie, > 10-year survival without evidence of disease) is achieved in at least 17% of resected patients. Candidates for resection include those with limited and in some cases extensive hepatic disease, and in highly selected cases, patients with extrahepatic disease. Number, size, and bilaterality of CLMs no longer stand as absolute contraindications to surgery. Chemotherapy has further advanced the field of surgery for CLMs, enabling an additional group of patients who present with unresectable disease to undergo surgery after downsizing with chemotherapy. Modern surgical techniques and liver preparation allow resection after chemotherapy, with excellent results. This article summarizes the current multidisciplinary approach to treatment of CLMs. The definition of resectability, conversion of unresectable CLMs to resectable ones, advances in surgical techniques, advances in chemotherapy, and predictors of outcome are detailed

Aims To evaluate the role of routine laparoscopy as a staging modality prior to laparotomy and hepatic resection for metastatic colorectal cancer. Methods Prospectively collected data were analysed from a database. In the first half of the series patients underwent selective laparoscopy before proceeding to laparotomy and in the second part of the series laparoscopy was used routinely. Patients undergoing laparotomy directly were analysed in Group 1 and those having laparoscopy before laparotomy in Group 2. The ability of laparoscopy to pick up unresectable and extrahepatic disease, resectability rate and open and close laparotomy rate were recorded. Results Of the 284 patients, 74 were in Group 1 (no laparoscopy) and 210 in Group 2 (laparoscopy as standard). The resectability rate was 81% in Group 1 and 87% in Group 2. The open and close laparotomy rate was 19% and 8%, respectively (p = 0.025). In Group 2 alone, laparoscopy identified 39% of unresectable disease and prevented an open and close procedure. Conclusions Routine use of staging laparoscopy increases the resectability rate and reduces the inoperability rate in these patients.

Chemoradiation is a standard approach to advanced unresectable head and neck cancer, although the optimum combination regimen remains controversial. However, in the past few years, chemoradiation has been successfully extended from the treatment of unresectable disease to the postsurgical therapy of high-risk patients and its value as an organ preservation procedure is under evaluation. More recently, molecular-targeted therapies have emerged, which interfere with mechanisms of chemo- and radioresistance, and preliminary data are promising. Their use in the combined treatment of head and neck cancer will hopefully further improve the value of chemoradiation in the clinical setting.

Background The aim of this study was to observe the effects of neoadjuvant therapy with irinotecan and5-fluorouracil (5-FU)/folinic acid (FA) on the resection rate and survival of colorectal cancer patients with initially unresectable hepatic metastases. Patients and methods Forty patients received neoadjuvant chemotherapy comprising irinotecan 180 mg/m2 administered intravenously (i.v.) on day 1, FA 200 mg/m2 i.v. on days 1 and 2, 5-FU 400 mg/m2 i.v. bolus on days 1 and 2, and 5-FU 1200 mg/m2 as a continuous 48-h i.v. infusion on day 1. The treatment was repeated every 2 weeks and response was assessed every 12 weeks (six cycles). Results The objective response rate to chemotherapy was 47.5% (n = 19), with two complete responses and disease stabilization in 11 (27.5.%) patients. Responses were unconfirmed for 11 patients undergoing surgery within 2 weeks. Treatment was well tolerated and adverse events were typical of the chemotherapy agents used. Twenty-seven (67.5%) patients reported hematological toxicity (35.0% grade 3/4) and 14 (35.0%) reported gastrointestinal toxicity (12.5% grade 3/4). Thirteen patients (32.5%) underwent potentially curative liver resection following chemotherapy. Chemotherapy was particularly effective in patients with large metastases on entry to the study. The median time to progression is 14.3 months and, at a median follow-up of 19 months, all patients are alive. Conclusions Neoadjuvant therapy with irinotecan combined with 5-FU/FA enabled a significant proportion of patients with initially unresectable liver metastases to undergo surgical resection. The effects of treatment on survival have yet to be determined.

Historically, the application of chemotherapy in patients with squamous cell head and neck cancer had been limited to the palliative setting; however, the role of chemotherapy in the definitive management of these tumors has undergone great evolution during the last 5 to 10 years. Available randomized data currently support a role for chemotherapy as part of combined modality, curative treatment strategies in the management of patients with unresectable disease, advanced nasopharynx cancer, and as part of a larynx preservation approach in patients with advanced larynx or hypopharynx cancer requiring total laryngectomy. Chemoprevention as a strategy to prevent second primary tumors also shows great promise.

e21053Background: According to current NCCN guidelines, melanoma patients with metastatic or unresectable disease should be tested for BRAF V600 mutations to evaluate therapy options. Test adoption...

226 Background: Staging laparoscopy (SL) has been shown to be useful in extrahepatic biliary tumors (EHBTs) to avoid unnecessary laparotomies in unresectable disease. However, the added value of SL for EHBTs has not been well characterized in the era of modern imaging. Methods: We reviewed patients from ten institutions who underwent attempted resection of EHBTs between 1998 and 2015, including gallbladder, distal, and hilar subtypes. Yield of laparoscopy = (Number of positive SL / Total number of SL). Accuracy of laparoscopy = (Number of positive SL / Patients with unresectable disease). These data were compared by use of the chi-squared test and significance was p

Inflammatory myofibroblastic tumors (IMTs) are indolent mesenchymal neoplasms associated with a small risk of aggressive behavior and metastasis. Surgery is the mainstay of treatment and until recently there have been limited effective treatment options for unresectable disease. This review describes the identification of anaplastic lymphoma kinase (ALK) fusion genes in approximately 50% of IMTs and the role of ALK inhibition in the treatment of this disease.A recent phase I dose-escalation trial of the selective MET/ALK inhibitor crizotinib showed a long-term partial response in a patient with IMT carrying an ALK translocation but not in a patient with ALK-negative disease. Emergence of resistance to crizotinib occurs approximately 5-8 months after initiation of therapy and has been shown to be driven by different mechanisms. Multiple second-generation ALK inhibitors are currently being investigated in the preclinical and clinical trial setting.ALK-directed therapy has emerged as a highly effective treatment option for a subset of patients with IMT and pulmonary adenocarcinoma. A number of additional malignancies, including rhabdomyosarcoma, neuroblastoma, anaplastic large cell lymphoma, renal cell carcinoma, and inflammatory breast cancer, have been shown to activate ALK expression by means of ALK fusion proteins, ALK mutations, or increased ALK copy number. Development of more selective ALK inhibitors, which can overcome emergent crizotinib resistance mutations, as well as development of combination treatments with drugs targeting compensatory pathways, will be key to achieving therapeutic success in targeting this potent and prevalent oncogenic driver.

Malignant perivascular epithelioid cell tumor (PEComa) was a kind of rare disease with malignant behavior and poor prognosis. Nearly all PEComas show immunoactivity for HMB45. The treatment strategy for malignant PEComa is still of controversy, especially in advanced or unresectable disease. We reported a 14-year-old patient of unresectable malignant PEComa, who was treated with multiple combined chemotherapies. The patient died of tumor 9 months after surgery, although 3 different combined chemotherapeutic regimens and antiangiogenic drug were used. Our case suggested that empirical chemotherapeutic regimens for soft tissue sarcomas might not be suitable for PEComa.

Metastatic or unresectable disease is identified in approximately20% of patients presenting with invasive urothelial cancer. Inaddition, up to 50% of patients will develop metastases followingradical cystectomy for clinically localized disease. Multiagentcisplatin-based chemotherapy is considered standard first-linetreatment for these patients. Although urothelial cancer is considereda chemosensitive tumour, metastatic disease is associatedwith poor prognosis and short-term survival. Here, we review therole of a multidisciplinary approach to treating patients with metastaticurothelial cancer.

Current treatment of malignant melanoma exemplifies not only the need for translational research but also many of the challenges of moving from bench to bedside. Melanoma remains unique among solid tumors in that its treatment primarily is surgical. Radiation is of limited benefit, and chemotherapy has been disappointing in both the adjuvant and metastatic settings. This leaves clinicians with few options for reducing the chance of recurrence after surgery and for treating unresectable disease. With this in mind, there has been a fervent attempt to identify novel approaches to melanoma therapy and translate them into clinical use.

Objective To evaluate the predictive value of conventional criteria for identifying surgically unresectable disease among patients with ovarian cancer undergoing initial operative intervention at tertiary referral centers employing a so-called aggressive approach to surgical cytoreduction. Methods All patients with advanced epithelial ovarian cancer undergoing primary surgery between August 1997 and August 2006 were identified. Surgical/pathological documentation of disease extent pre/post-cytoreduction was extracted from the medical record retrospectively. All patients meeting conventional criteria for unresectable disease criteria (ascites>1000 mL, omental extension to spleen >1 cm, parenchymal liver disease >1cm, porta hepatis involvement >1 cm, diaphragmatic disease >1 cm, carcinomatosis >1 cm, and suprarenal adenopathy >1 cm) were selected for further study. Results A total of 180 consecutive patients had disease meeting conventional criteria for unresectability at=1 site(s). Optimal cytoreduction (residual disease=1 cm) was achieved in 166 patients (92.2%). Optimal resection rates according to the most common individual unresectable disease criteria were as follows: ascites >1000 mL=91.3% (116/127), carcinomatosis >1 cm=91.0% (81/89), and splenic involvement >1 cm=84.9% (45/53). For patients with ascites >1000 mL alone, optimal cytoreduction was achieved in 95.8% (46/48) of cases. Optimal resection rates according to the total number of unresectable disease sites were as follows: 1 site=95.0% (19/20), 2 sites=93.8% (61/65), 3 sites=81.5% (22/27), 4 sites=93.3% (14/15), and 5 sites=80.0% (4/5). Conclusions These data suggest that commonly accepted criteria of surgically unresectable disease for women with advanced ovarian cancer lack the necessary precision to guide clinical management. Pre-operative assessment of resectability should be made by an experienced surgical team prior to deferring the initial attempt at surgical cytoreduction.

e20109 Background: Unresectability is a frequent inclusion criterion for clinical trials in metastatic melanoma. However, no consensus definition of unresectability exists. In OPTiM, a phase 3 tria...

Cytoreductive surgery combined with intraperitoneal chemotherapy can improve survival in appropriately selected patients with colorectal peritoneal metastases. Outcomes are best in those patients in whom a complete cytoreduction can be achieved. Unresectable disease is however encountered in approximately one-quarter of patients at laparotomy. The merits, or otherwise, of proceeding with an incomplete cytoreduction in this setting are unclear. We performed a review of published outcomes following incomplete cytoreduction for colorectal peritoneal metastases. Using the electronic databases, PubMed and MEDLINE, a systematic search of available literature published during the period January 1997 to September 2014 was conducted. Following application of exclusion criteria, 19 papers were identified and included in this review. These comprised fifteen case series, 3 case control studies and one randomised control trial. In the nineteen studies included in this review, 2790 patients underwent cytoreductive surgery with or without intraperitoneal chemotherapy for peritoneal metastases of colorectal origin. Of these, 1732 (62%) underwent a complete cytoreduction while 986 (35%) patients underwent an incomplete cytoreduction. Median survival in the complete cytoreduction group ranged from 11 to 62 mo while survival in the latter group ranged from 2.4 to 32 mo. Of the 986 patients with an incomplete cytoreduction, 331 patients received intraperitoneal chemotherapy and survival in this cohort ranged from 4.5 to 32 mo. An incomplete cytoreduction, with or without intraperitoneal chemotherapy, does not appear to confer a survival benefit. The limited available data points to a palliative benefit in a subset of patients. In the absence of high quality data, the decision as to whether or not to proceed with surgery should be made on an individual patient basis.

Liposarcoma (LPS) is the most common type of soft-tissue sarcoma. Complete surgical resection is the only curative means for localized disease; however, both radiation and conventional cytotoxic chemotherapy remain controversial for metastatic or unresectable disease. An increasing number of trials with novel targeted therapy of LPS have provided encouraging data during recent years. This review will provide an overview of the advances in our understanding of LPS and summarize the results of recent trials with novel therapies targeting different genetic and molecular aberrations for different subtypes of LPS.

Contains fulltext : 52974.pdf (Publisher’s version ) (Closed access) Radiofrequency ablation (RFA) for liver metastasis of colorectal (H-CRC) origin is a well-documented technique in surgically unresectable disease. Overall recurrence figures appear inferior to resection but are based on a selection of patients with unresectable disease, often due to multiple localisations of extensive disease. Lesion based recurrence is probably more appropriate to predict results of RFA in surgically resectable H-CRC and figures may be good enough to consider RFA an alternative treatment in high risk patients.

The management of hepatic malignancies, primary or metastatic, is an increasingly common problem in clinical practice. Unfortunately, most patients present with unresectable disease for which there is no universally accepted standard therapy. Radiotherapy is gaining importance in the management of these tumors and in this article we will review the advancements made in this field recently. Increased understanding of the relationship between radiation dose and volume and the risk of radiation-induced liver disease (RILD) has allowed delivery of high-dose focal liver radiation with encouraging results. A recent US phase II trial suggests a radiation dose-dependent improvement in survival when compared to historical controls. Others have reported favorable experience with moderate-dose external-beam radiotherapy, stereotactic hypofractionated radiotherapy, and radiopharmaceuticals.

4264 Introduction: Gastric cancer is more common in undeveloped countries, the only potentially curative treatment is surgery, a survival of 5-6 months in unresectable disease, neoadjuvant chemotherapy could be useful to achieve surgery.

Treatment of pancreatic cancer remains a challenging task that often requires a multidisciplinary approach to confer optimal response and, ideally, maximize survival. A combination of locoregional approaches such as surgery and radiotherapy, along with systemic therapies for eradication of micrometastases, should be considered both for patients who are operative candidates and for those with locally advanced, unresectable disease. How best to combine these modalities in terms of schedule, timing, and choice of agents is a question that continues to be actively investigated. Some of these data are equivocal or conflicting; thus standards of care for combined-modality treatment have not been uniformly accepted to date. This article provides an overview of combined-modality therapy, focusing on the major studies that have guided our current approach to the treatment of pancreatic cancer and examining new strategies that are likely to improve outcomes and survival for patients in the future.