Chance Of Long-term Survival Research Articles

Long-term survival and cure model following liver resection for breast cancer metastases

IntroductionLong-term survival is still rarely achieved with current systemic treatment in patients with breast cancer liver metastases (BCLM). Extended survival after hepatectomy was examined in a select group of BCLM patients.Patients and methodsHepatectomy for BCLM was performed in 139 consecutive patients between 1985 and 2012. Patients who survived < 5 years were compared to those who survived ≥ 5 years from first diagnosis of hepatic metastases. Predictive factors for survival were analyzed. Statistically cured, defined as those patients who their hazard rate returned to that of the general population, was analyzed.ResultsOf the 139, 43 patients survived ≥ 5 years. Significant differences between patient groups (< 5 vs. ≥ 5 years) were mean time interval between primary tumor and hepatic metastases diagnosis (50 vs. 43 months), mean number of resected tumors (3 vs. 2), positive estrogen receptors (54% vs. 79%), microscopic lymphatic invasion (65% vs. 34%), vascular invasion (63% vs. 37%), hormonal therapy after resection (34% vs. 74%), number of recurrence (40% vs. 65%) and repeat hepatectomy (1% vs. 42%), respectively. The probability of statistical cure was 14% (95% CI 1.4–26.7%) in these patients.ConclusionsHepatectomy combined with systemic treatment can provide a chance of long-term survival and even cure in selected patients with BCLM. Microscopic vascular/lymphatic invasion appears to be a novel predictor for long-term survival after hepatectomy for BCLM and should be part of the review when discussing multidisciplinary treatment strategies.

Clinical relevance of oncologic prognostic factors in the decision-making of pre-hepatectomy chemotherapy for colorectal cancer hepatic metastasis: the priority of hepatectomy

BackgroundAlthough liver resection (LR) provides the best chance of long-term survival for patients with colorectal cancer (CRC) hepatic metastasis, concerns regarding chemotherapy before liver resection remain unresolved.MethodsA retrospective review of patients who underwent curative LR for CRC hepatic metastasis between January 2008 and February 2016 was performed. Outcome relevance based on oncologic prognostic factors and chemotherapy prior to liver resection was assessed.ResultsPatients who had received pre-hepatectomy chemotherapy for CRC hepatic metastasis and delayed liver resection had a worse outcome in terms of CRC recurrence following liver resection. The hazard ratio (HR) of pre-hepatectomy chemotherapy in patients with minor oncologic prognostic factors was 1.55 (confidence interval, CI = 1.07–2.26, p = 0.021) for CRC recurrence after liver resection for hepatic metastasis, whereas the HR of pre-hepatectomy chemotherapy was 1.34 (CI = 0.99–1.81, p = 0.062) for CRC recurrence in patients with multiple oncologic prognostic factors.ConclusionThe administration of pre-hepatectomy chemotherapy and delaying liver resection seems not to be an optimal strategy to provide a clinical benefit for patients with CRC hepatic metastasis. Hence, liver resection should be attempted without delay at the initial detection of CRC hepatic metastasis whenever possible.

A retrospective review of correlative radiological assessment and surgical exploration for hilar cholangiocarcinoma.

Backgrounds/AimsHilar cholangiocarcinomas (HCCAs) are tumors that involve the biliary confluence; at present, radical surgery offers the only chance of long-term survival, but this can be challenging given the complexity of the hilar anatomy. Blumgart and Jarnagin described a preoperative staging system that incorporates the effect of local tumor extent and its impact on adjacent structures and that has been demonstrated to correlate better with actual surgical resectability. The primary aim of this study is to describe the correlation between preoperative Blumgart-Jarnagin staging and its correlation with surgical resectability.MethodsPatients who underwent surgical resection for hilar cholangiocarcinoma at Singapore General Hospital between January 1, 2002, and January 1, 2013, were identified from a prospectively maintained institutional database. All patients were staged based on the criteria described by Blumgart and Jarnagin. Correlation with surgical resectability was then determined.ResultsA total of 19 patients were identified. Overall resectability was 57.8% (n=11). Patients with Blumgart-Jarnagin stage T1 had the highest rates of resectability at 80%; patients with stage T2 and T3 disease had resectability rates of 25% and 40% respectively. Median overall survival was 13.6 months.ConclusionsThe Blumgart-Jarnagin staging system is useful for predicting tumor resectability in HCCA.

Growing teratoma syndrome presented as a left forearm mass: A case report.

Growing teratoma syndrome (GTS) is a rare disease occurring in patients with non-seminomatous germ cell tumors (NSGCT), which is characterized by enlarging masses in the presence of normal tumor markers either during or after completion of chemotherapy. The disease is chemo-resistant and radio-resistant and complete surgical removal offers the best chance of long-term survival. GTS was first described by Logothetis et al. in 1982, who designated criteria to diagnose this rare entity [1]. The fact that GTS is not common leads to delays in diagnosis and surgical intervention. This case report refers to a testicular growing teratoma with its first clinical manifestation being a gigantic forearm mass.

The paradigm of tumor shrinkage and rapid liver remnant hypertrophy for conversion of initially unresectable colorectal liver metastasis: a case report and literature review

BackgroundFor colorectal liver metastasis (CRLM) patients, hepatic resection is currently the sole cure offering the chance of long-term survival. Tumor shrinkage and planned liver remnant hypertrophy are the two key strategies for conversion of initially unresectable CRLM. First conducted in 2012, associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) allows rapid liver growth. As a means to induce hypertrophy, portal vein embolization (PVE) has been widely applied before extending hepatectomy. Recently, Peng et al. present a new approach of terminal branches portal vein embolization (TBPVE), offering an efficient way to amplify FLR and making chances for surgery in 2 weeks.Case presentationWe reported a 61-year-old woman with synchronous hepatic metastasized carcinoma of the colon sigmoideum underwent TBPVE after 6 cycles of neoadjuvant therapy in order to perform a planned right trisectionectomy. Rapid liver remnant hypertrophy and remarkable tumor shrinkage were achieved, and laparoscopic sigmoidectomy and right trisectionectomy were successfully performed. The postsurgical course was uneventful and 7 months of recurrence-free survival have been witnessed.ConclusionsThe dual tactics of tumor shrinkage and planned rapid liver remnant hypertrophy will make concerted efforts to further increase the clinical candidacy for curative resection, which are valuable for further investigation.

Major Histocompatibility Mismatch and Donor Choice for Second Allogeneic Bone Marrow Transplantation

Large alternative donor pools provide the potential for selecting a different donor for a second allogeneic (allo) bone or marrow transplant (BMT). As HLA disparity may contribute to the graft-versus-tumor effect, utilizing new mismatched haplotype donors may potentially improve the antitumor activity for relapsed hematologic malignancies despite a previous alloBMT. Data from patients who received a second alloBMT for relapsed hematologic malignancies at Johns Hopkins were analyzed. Outcomes were compared between patients who received a second allograft with the same MHC composition and those who received an allograft with a new mismatched haplotype. Loss of heterozygosity analysis was performed for patients with acute myeloid leukemia (AML) whose first allograft was haploidentical. Between 2005 and 2015, 40 patients received a second BMT for a relapsed hematologic malignancy. The median follow-up is 750 (range, 26 to 2950) days. The median overall survival (OS) in the cohort is 928 days (95% confidence interval [CI], 602 to not reached [NR]); median event-free survival (EFS) for the cohort is 500 days (95% CI, 355 to NR). The 4-year OS is 40% (95% CI, 25% to 64%), and the 4-year EFS is 36% (95% CI, 24% to 55%). The cumulative incidence of nonrelapsed mortality by 2 years was 27% (95% CI, 13% to 42%). The cumulative incidence of grade 3 to 4 acute graft-versus-host disease (GVHD) at 100 days was 15% (95% CI, 4% to 26%); the cumulative incidence of extensive chronic GVHD at 2 years was 22% (95% CI, 9% to 36%). The median survival was 552 days (95% CI, 376 to 2950+) in the group who underwent transplantation with a second allograft that did not harbor a new mismatched haplotype, while it was not reached in the group whose allograft contained a new mismatched haplotype (hazard ratio [HR], .36; 95% CI, .14 to .9; P = .02). EFS was also longer in the group who received an allograft containing a new mismatched haplotype, (NR versus 401 days; HR, .50; 95% CI, .22 to 1.14; P = .09). Although the allograft for this patient's second BMT contained a new mismatched haplotype, AML nevertheless relapsed a second time. Second BMTs are feasible and provide a reasonable chance of long-term survival. An allograft with a new mismatched haplotype may improve outcomes after second BMTs for relapsed hematologic malignancies.

P-300 - Retrospective clinicopathological analysis of colon and rectal neuroendocrine tumors

Introduction: Colorectal cancer is the second most common cause of cancer death after gastric cancer in Uzbekistan. A little number of colorectal neoplasms made up by neuroendocrine tumors (NET). Neuroendocrine tumors of the colon and rectum represent a broad clinical-pathologic spectrum with varying morphologic features and biological behavior. The aim of present study is to analyze pathological and clinical features of NET which have not been studied in Uzbekistan before. Methods: Study included 54 patients with colorectal NEN who were treated in National Cancer Research Center, between 2006 and 2011. In total, 36 (66.7%) patients were men and 18 (33.3%) were women, with a mean age of 56.4 years. The collected clinicopathological data were: patients' age, sex, tumor size, tumor location, pathological diagnosis based on WHO 2010 criteria, depth of tumor invasion, mitotic index [<2/10 high power fields (HPF), 220/10 HPF, or >20/10 HPF], Ki-67 labeling index (≤2, 320, or >20%), responses to treatment (operative procedure, chemotherapy or radiotherapy), metastases, and survival. Results: Tumor located in the rectum was observed in 44 (81.5%) cases, in 2 (3.7%) cases tumor was found in colon, and 8 (14.8%) patients had tumor in appendix. Morphologically, NET G1 – 30 (55.6%) cases, G2 – 12 (22.2%) cases, NEC (G3) – 8 (14.8%), and mixed adeno-neuroendocrine carcinoma (MANEC) was found in 4 (7.4%) cases. Of 54 patients, 18 underwent mucosectomy, and 36 were surgically resected with lymph node dissection. As for tumor size, the mean size was 21.7 mm, and 21 tumors (38.9%) were smaller than 10 mm. Most tumors were limited within mucosa or submucosa (44 cases, 81.5%), showed mitosis in <2/10 HPF (41 cases, 75.9%), and had a Ki-67 index of ≤2% (38 cases, 70.4%). Compared with rectal NENs, colonic NENs more frequently exhibited larger tumor size (P < 0.0001) and distant metastasis (P < 0.0001). Colonic NENs had a worse prognosis (P = 0.0027), with 5-year overall survival rates of 66.7% versus 88.1%. NET, NEC, and MANEC were noted in 61.8%, 23.5%, and 14.7% of patients, respectively. Palliative chemotherapy or radiotherapy did not improve survival rates in patients, who had distant metastasis at the time of diagnosis. However, noticed improvement in patients condition with stage IIA rectal small cell neuroendocrine carcinoma whom administered adjuvant chemotherapy with cisplatin and etoposide at our hospital. Conclusion: Retrospective analysis indicated that tumor size and pathological classification were associated with the prognosis. The worse outcome of colonic NENs observed in clinical practice might be due to not only to biological differences, but also to larger tumor size in colonic NENs. Surgical treatment remains major approach in NENs' therapy, whereas aggressive adjuvant chemotherapy with cisplatin and etoposide might offer a better chance of long-term survival for patients with stage II neuroendocrine carcinomas in the colon and rectum, which deserves further investigation.

An Amazonian rainforest and its fragments as a laboratory of global change.

We synthesize findings from one of the world's largest and longest-running experimental investigations, the Biological Dynamics of Forest Fragments Project (BDFFP). Spanning an area of ∼1000 km2 in central Amazonia, the BDFFP was initially designed to evaluate the effects of fragment area on rainforest biodiversity and ecological processes. However, over its 38-year history to date the project has far transcended its original mission, and now focuses more broadly on landscape dynamics, forest regeneration, regional- and global-change phenomena, and their potential interactions and implications for Amazonian forest conservation. The project has yielded a wealth of insights into the ecological and environmental changes in fragmented forests. For instance, many rainforest species are naturally rare and hence are either missing entirely from many fragments or so sparsely represented as to have little chance of long-term survival. Additionally, edge effects are a prominent driver of fragment dynamics, strongly affecting forest microclimate, tree mortality, carbon storage and a diversity of fauna. Even within our controlled study area, the landscape has been highly dynamic: for example, the matrix of vegetation surrounding fragments has changed markedly over time, succeeding from large cattle pastures or forest clearcuts to secondary regrowth forest. This, in turn, has influenced the dynamics of plant and animal communities and their trajectories of change over time. In general, fauna and flora have responded differently to fragmentation: the most locally extinction-prone animal species are those that have both large area requirements and low tolerance of the modified habitats surrounding fragments, whereas the most vulnerable plants are those that respond poorly to edge effects or chronic forest disturbances, and that rely on vulnerable animals for seed dispersal or pollination. Relative to intact forests, most fragments are hyperdynamic, with unstable or fluctuating populations of species in response to a variety of external vicissitudes. Rare weather events such as droughts, windstorms and floods have had strong impacts on fragments and left lasting legacies of change. Both forest fragments and the intact forests in our study area appear to be influenced by larger-scale environmental drivers operating at regional or global scales. These drivers are apparently increasing forest productivity and have led to concerted, widespread increases in forest dynamics and plant growth, shifts in tree-community composition, and increases in liana (woody vine) abundance. Such large-scale drivers are likely to interact synergistically with habitat fragmentation, exacerbating its effects for some species and ecological phenomena. Hence, the impacts of fragmentation on Amazonian biodiversity and ecosystem processes appear to be a consequence not only of local site features but also of broader changes occurring at landscape, regional and even global scales.

Symptom Trajectories in Children Receiving Treatment for Leukemia: A Latent Class Growth Analysis With Multitrajectory Modeling

ContextCancer treatment symptoms play a major role in determining the health of children with cancer. Symptom toxicity often results in complications, treatment delays, and therapy dose reductions that can compromise leukemia therapy and jeopardize chances for long-term survival. Critical to understanding symptom experiences during treatment is the need for exploration of “why” inter-individual symptom differences occur; this will determine who may be most susceptible to treatment toxicities. ObjectivesThis study examined specific symptom trajectories during the first 18 months of childhood leukemia treatment. Symptom measures included fatigue, sleep disturbances, pain, nausea, and depression. MethodsSymptom trajectories of 236 children with leukemia three to 18 years old were explored prospectively over four periods: initiation of post-induction therapy, four and eight post-induction therapy, and the last time point was at the beginning of maintenance/continuation therapy. Latent class growth analysis was used to classify patients into distinctive groups with similar symptom trajectories based on patients' response patterns on the symptom measures over time. ResultsThree latent classes of symptom trajectories were identified and classified into mild, moderate, and severe symptom trajectories. The only demographic characteristic with a significant relationship to membership in the latent class symptom trajectories was race/ethnicity. All other demographic characteristics including leukemia risk levels showed no significant relationships. ConclusionThis study is unique in that groups of patients with similar symptoms were identified rather than groups of symptoms. Further research using latent class growth analysis is needed.

Colorectal cancer resection in the Australian nonagenarian patient.

The nonagenarian population is a rapidly growing segment of the Australian population. Surgical resection continues to offer the best chance of long-term survival in colorectal cancer. The primary aims of the present study were to evaluate the 30-day mortality and survival of Australian patients ≥90years of age undergoing surgical resection for colorectal cancer in our health service. The secondary aims were to examine the clinicopathological characteristics of the patients and their tumours. All patients ≥90years of age undergoing surgical resection for colorectal cancer from 1998 to 2012 were identified in a centralized multihospital database. Key clinicopathological data, 30-day mortality and long-term overall survival were recorded for each patient. There were 121 patients identified of median age 91years, 74% of whom were female. The median tumour size was 40mm, and 51% of operations were carried out as an emergency. The TNM stage was Stage I/II in 57%, Stage III in 40% and Stage IV in 3%. The 30-day mortality was 6.6% (eight of 121) and the 1-, 3- and 5-year overall survival rates were 82.6%, 50.2% and 32.3%, respectively. Surgical resection in the nonagenarian patient has an acceptable mortality and offers good overall survival.

АНАЛІЗ КОМБІНОВАНОГО ВПЛИВУ ІНТРАТУМОРАЛЬНОЇ ЕКСПРЕСІЇ ТИМІДИЛАТСИНТАЗИ ТА HENT1 НА ЕФЕКТИВНІСТЬ СХЕМИ ГЕМЦИТАБІН+ТЕГАФУР В АД’ЮВАНТОМУ ЛІКУВАННІ ХВОРИХ НА РАК ПІДШЛУНКОВОЇ ЗАЛОЗИ

Рак підшлункової залози (РПЗ) є одним із найагресивніших серед гастроінтестинальних раків. Шанс на довгострокову виживаність, що залишається неприйнятливо низькою, дає тільки радикальна резекція. Оптимізація ад’ювантного лікування хворих на РПЗ є актуальним питанням сучасної онкології. Метою роботи був аналіз комбінованого впливу інтратуморальної експресії hENT1 і тимідилатсинтази (TS) на ефективність схеми гемцитабін+тегафур ГемТег в ад'ювантному лікуванні хворих на РПЗ. До дослідження залучено 62 хворих на РПЗ з R0-cтатусом резекції на І та ІІ стадіях (UICC ver.7). Усі хворі отримували комбінацію ГемТег в якості ад’ювантної терапії. Діагноз у кожному випадку був веріфікований гістологічно, після чого імуногістохімічно визначали експресію hENT1 та TS. Статистичну обробку виконували за допомогою критерію Фішера, методів χі-квадрат, Каплана–Майєра та аналізу ризиків за Коксом. Медіана спостереження становила 34 місяці. За допомогою однофакторного аналізу оцінювали переваги у виживаності, порівняно з когортою хворих із співпаданням низької експресії hENT1 та TS. При цьому виживаність у когортах із високою експресією hENT1, з високою експресією TS та з високою експресією обох маркерів була значно вищою (р=0,053; р=0,03 та р&lt;0,001 відповідно). При багатофакторному аналізі ризиків за Коксом у стратифікованих когортах HR становив 4,65 (СI: 2,12–10,21), 4,82 (СI: 2,13–10,91) та 23,14 (СI: 2,73–195,88) відповідно. Висока інтратуморальна експресія hENT1 та TS незалежно одне від одного може покращувати загальну виживаність хворих на РПЗ при ад’ювантному лікуванні за схемою ГемТег. Хворі, в яких одночасно відзначалася висока експресія hENT1 та TS, отримували найбільшу перевагу в виживаності.

Method and significance of specimens standardized pathological treatment in pancreaticoduodenectomy for pancreatic head cancer

Pancreatic ductal adenocarcinoma is a highly aggressive disease with a grim prognosis. Surgical resection offers the best chance for long-term survival. Negative-margin resection still remains the goal, the influence of margin status on outcomes in pancreatic head carcinoma remains controversial, as conflicting data have been plagued by a lack of standardization in R0 resection and margin definitions, pathologic analysis, and reporting. In contrast to common belief, a high rate of R1 resections in pancreatic cancer is not a marker of low-quality surgery but rather of high-quality pathology. The international pathological consensus of pancreatic head carcinoma is still needed to fully understand the prognostic value of margin status in order to optimize treatment strategy for this disease.

Eight-Year Long-Term Survival of an Advanced Gastric Cancer Patient Treated by Multidisciplinary Therapy Including Repeated Surgery and Metronomic Chemotherapy

A 69-year-old male, who had gastric cancer with extensive intra-abdominal lymph node metastasis, received palliative distal gastrectomy. He underwent repeated resection of metachronous right and left adrenal metastatic lesions 2 years and 5.3 years after the initial operation, respectively. The patient also experienced right femoral bone metastasis and IVC tumour thrombus 2.9 years and 6.6 years after the initial surgery, which were treated by radiation therapy. The slowly progressive tumour status was maintained by continuation of metronomic chemotherapy including S-1 as a key drug, and a total of 8-year long-term survival was achieved. Although rare, some selected patients with advanced gastric cancer have a chance of long-term survival, like the current case. The efficacy of multidisciplinary therapy for far advanced gastric cancer patients, especially an important role of repeated surgery and metronomic chemotherapy, was discussed.

Suicide gene therapy of rhabdomyosarcoma.

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and young adulthood. Conventional treatment consisting of surgery, chemotherapy and radiotherapy can be insufficient, as long-term survival chances decrease dramatically when cancer recurrence occurs. Due to this fact, efficient treatment of this cancer is still a demanding issue, thus, novel and innovative therapies have to be considered as a part of combined treatment. In the present study, we present effective suicide gene therapy of rhabdomyosarcoma cell line Rh30 involving herpes simplex thymidine kinase (HSV-TK) and ganciclovir (GCV). Transduction of rhabdomyosarcoma cells using lentiviral vectors allowed efficient introduction of HSV-TK gene. In this study we proved high susceptibility of modified cells to ganciclovir resulting in eradication of cancer cells both invitro and invivo. Our data revealed strong gap junctional intercellular communication in examined cell line responsible for elimination of unmodified cells by bystander effect, even if HSV-TK-expressing cells comprise only 20% of cultured cells. Moreover, investigated approach is also efficient invivo, where complete remission of tumors upon only 14 days of systemic administration of GCV can be observed. Obtained results suggest that HSV-TK suicide gene therapy is very promising concept in future clinical studies concerning rhabdomyosarcoma.

Early Allogeneic Blood Stem Cell Transplantation after Melphalan-Induced Aplasia for Patients with Primary Refractory or Relapsed Acute Myeloid Leukemia - Results of a Retrospective Single Center Analysis

IntroductionPatients (pts) with acute myeloid leukemia (AML) and induction failure or relapse have a dismal prognosis. In 2010 we started to offer an allogeneic transplantation (tx) in aplasia to all eligible patients with an HLA-compatible donor as soon as possible after diagnosis of refractory or relapsed AML. Here we report the results of a retrospective analysis.Patients and treatment25 pts (median age 51; 24-71) received an allogeneic tx in aplasia. Diagnoses were primary AML in 20 pts, t-AML in 3 and s-AML in 2 patients. 20 pts were transplanted because of primary refractory AML, in 5 pts the indication was relapsed AML. ELN classification was favorable in 3 (all NPM pos), intermediate-1 in 7, intermediate-2 in 4 and adverse in 11 pts. First induction therapy consisted of daunorubicin and Cytarabin (3+7) in all but one pt. A second induction with high-dose Cytarabin was given in 9/20 pts with induction failure. The search for a stem cell donor was started immediately after results of high-risk cytogenetic, no achievement of bone marrow aplasia on day 14 of induction therapy or in case of induction failure. Four patients had a related 10/10 donor, for 11 patients a 10/10 matched unrelated donor was identified and 10 patients received a transplant from a 9/10 unrelated donor. The interval between diagnosis and tx was 3 (1-4) months (mo) for patients with primary refractory AML as well as relapsed AML. In 21 patients melphalan (100-140 mg/m²) was used to induce an aplasia before starting conditioning therapy. The interval between melphalan and conditioning therapy was 13 (9-21) days. 3 pts started the conditioning therapy while in aplasia after previous chemotherapy. The conditioning therapy was of reduced intensity in all pts. and consisted of Treosulfan (30g/m²)/Fludarabin in 18 pts, TBI(8Gy)/Fludarabin in 5 pts and Busulfan(8m/(kg)/Fludarabin in 2 pts, respectively. Most pts (17/25) had a severe neutropenia below 0,5/nl (med 0,2; 0,1-5,2) before starting melphalan because of refractory leukemia.ResultsAfter a median follow-up of 31 (10-60) mo 6 pts (24%) are alive without relapse. 5 (20%) pts died because of a relapse after a median of 6 (2-18) mo. The non-relapse mortality was 44% (14/25 pts). Most of these pts (9/19, 47%) died because of infectious complications early after transplantation (med 1; 0-11) mo). Two patients developed pulmonary toxicity and died 1, respectively 19 mo after tx. In 3 pts acute gvhd was the main cause of mortality. The results for patients with 10/10 or 9/10 donors were comparable.ConclusionIn this retrospective "real-life" analysis we showed that an early allogeneic transplantation is feasible for patients with primary refractory and relapsed AML. A reduced intensity conditioning after induction of aplasia with melphalan offers a chance of long-term relapse-free survival for about a quarter of patients with an otherwise dismal prognosis. NRM is high, especially because of infectious complications early after transplantation, probably related to the long period of severe neutropenia. Therefore, the focus has to be set on early recognition and intervention of infectious complications. DisclosuresNo relevant conflicts of interest to declare.

Second Blood or Marrow Transplant (BMT) for Relapse: Mismatch Haplotype Switch May Improve Outcome

Introduction: With improvements in supportive care, including graft-versus-host disease (GVHD) control, relapse has become the major complication of allogeneic BMT. The use of haploidentical donors often allows the potential to select a different donor for the second transplant. We examined the outcomes of patients who underwent a second BMT for relapse at Johns Hopkins between 2005 and 2014. We hypothesized that if loss of heterozygosity is a mechanism for relapse after haploBMT, then utilizing a donor that recognizes the other shared haplotype could improve antitumor activity and thus overall survival (OS). In the case of a failed matched transplant, recognition of a non-shared haplotype on the tumor by the second allograft would be beneficial.Methods: We identified all patients who received a second transplant for relapse of a hematologic malignancy between 2005 and 2014. Acute GVHD (aGVHD) is reported as Glucksberg grades 1-4; chronic GVHD (cGVHD) is reported as limited or extensive. GVHD and non-relapse mortality (NRM) was calculated via cumulative incidence (CI) with competing risk analysis. OS was calculated as the time from second transplant to death or last known follow-up and estimated using the Kaplan Meier method. Differences in time to death between patient groups were estimated using Cox proportional hazards models. Non-relapse mortality was estimated using Fine and GrayÕs method.Results: Between 2005 and 2014, 40 patients received a second BMT for a relapsed hematologic malignancy (Table 1). The median age at second transplant was 43.9 (range 1 to 74); 14 (35%) were female. Fifteen (41%) received myeloablative conditioning for their first transplant, and 35 (92%) received high dose post-transplant cyclophosphamide (PTCy) as part of their GVHD prophylaxis. The incidence of grade 2-4 aGVHD after the first transplant was 13%, and limited cGVHD was 13%. There was no extensive cGVHD.Re-induction therapy and second allograft characteristics (Table 2): Refractory or progressive disease at the time of second transplant was present in 20% of patients, and 7/40 (18%) had their second transplant within 1 year. After a first failed HLA-matched transplant, 15 received a haploidentical graft, and 4 received a second HLA-matched graft. Among the 21 who relapsed after a haploBMT, 7 received an HLA-matched allograft, and 14 received a haploidentical graft; 6 out of those 14 used a donor that switched the shared haplotype. Most (81%) received PTCy with the second BMT.Median follow up is 598 days. Median OS in the cohort is 911 days (95% CI 602 Ð NR); 4 year OS is 38%. The CI of NRM by 2 years was 29% - 4 patients died of complications of GVHD (only one of whom received post-transplant Cyclophosphamide), 3 associated with prolonged cytopenias, 1 within a month of BMT, and 3 of pneumonia. Grade 2-4 aGVHD occurred in 11 pts (28%), grade 3-4 in 5 (13%). Extensive cGVHD was seen in 7 (18%).Median OS for the patients who relapsed after initial haploBMT who were then retransplanted with an HLA-haploidentical donor with a different shared haplotype has not been reached, versus a median OS of 501 [317-2950+] days among the 15 who did not receive a graft with an alternate shared haplotype (HR 0.21 [0.03, 1.61]; p=0.06). If the 19 patients who received a matched allograft at first transplant are included, median OS is 552 days in the group transplanted with a second graft with the same shared haplotype(s), and 1308 days (Figure 1) in the group whose allograft contained a different non-shared haplotype (HR 0.39 [0.16, 0.98]; p=0.04).OS was better when the second transplant was performed more than one year after the first (HR 0.30 [0.11, 0.80]; p=0.03). A trend towards improved OS was associated with disease status at time of second transplant (remission or chemo-responsiveness versus progressive or refractory disease; HR 0.41 [0.16, 1.03]; p=0.07). Source of graft (BM versus peripheral), conditioning intensity, era of transplant (2005-2010 versus 2010-2015), same versus different donor, and age group (<25, 25-60, 60+) did not significantly influence OS.Conclusion: Second transplants are feasible in all age groups and provide a reasonable chance of long-term survival. GVHD rates using PTCy are low, and similar to that seen with first BMTs. An allograft sharing a different haplotype in the case of relapse after haploBMT, or a haploidentical donor after failure of a matched graft, may be beneficial. [Display omitted] [Display omitted] [Display omitted] DisclosuresBrodsky:Apellis Pharmaceuticals Inc: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Achillion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Intravenous and intraperitoneal paclitaxel with S-1: new hope for patients with pancreatic cancer and peritoneal metastases?

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis with a 5-year survival rate still below 7% (1) and is predicted to become the second leading cause of cancer-related mortality within the next two decades (2). Surgical resection in combination with systemic therapy offers the only chance of long-term survival or cure (3). However, at diagnosis only 10–20% of patients have resectable tumors, 30–40% have locally advanced borderline-resectable or unresectable tumors, and the majority of 50–60% of patients present with metastatic disease, frequently with peritoneal metastases (1). Patients with peritoneal metastases have an extremely poor prognosis with survival rates ranging from weeks to several months dependent on the extent of the disease, performance status, and therapy. Peritoneal metastases are frequently associated with severe complications such as intestinal obstruction, massive ascites, and malnutrition. These complications result in a poor performance status and hamper the administration of chemotherapy. Moreover, systemically administered chemotherapeutic drugs may not reach sufficient concentrations in the peritoneal cavity and in peritoneal nodules for effective treatment of peritoneal metastases. More effective treatment strategies for peritoneal metastases are, therefore, one of the most pressing needs in the fight against pancreatic cancer.

Outcomes of hepatic resection for hepatocellular carcinoma with major portal or hepatic vein tumor thrombosis: retrospective cohort study

Background: Major vascular invasion by hepatocellular carcinoma (HCC) is a poor prognostic factor. The outcome of hepatic resection for this advanced stage tumor remains unclear. Objectives: To clarify the outcome of hepatic resection for HCC with vascular invasion. Methods: Between January 2005 and May 2013, 13 of 272 patients who underwent hepatic resection of HCC had a confirmed major portal or hepatic vein tumor thrombosis. The perioperative and long-term outcomes of this cohort of patients were retrospectively reviewed. Results: Ten of the 13 patients underwent preoperative transarterial chemoembolization (TACE). None showed tumor progression or liver function deterioration. All underwent hepatic resection with complete removal of tumor thrombus. The vascular resection margin was microscopically negative in all patients. Postoperative complications occurred in 62%. Most complications were pleural effusion, which necessitates percutaneous drainage. No perioperative mortality occurred. The median follow up time was 38.5 months (range 10–112). The median overall survival was 38.5 months. The 1-, 3-, and 5-year recurrence free survival was 93%, 36%, and 36%, respectively. The 1-, 3-, and 5 year-overall survival was 93%, 76%, and 48%, respectively. Nine patients had intrahepatic tumor recurrence, extrahepatic recurrence, or both. Five with recurrence underwent TACE, radiofrequency ablation, or surgical resection. On univariate analysis, the only factor that tended to relate to worse overall survival was underlying liver cirrhosis (P = 0.056). Conclusions: Hepatic resection for HCC with invasive thrombosis, combined with careful patient selection, close postoperative follow up, and early treatment of recurrence offers a chance of long-term survival. Keywords: Hepatocellular carcinoma, preoperative TACE, surgical resection, survival outcomes, tumor thrombus

Understanding the Paradigm Shift in Pancreatic Cancer.

Pancreatic adenocarcinoma is the fourth most deadly cancer in the United States and carries a grim prognosis. Surgical resection remains the only way to cure pancreatic cancer. It is a difficult surgery, requiring specialty hospitals for the best chance for immediate and long-term survival. Recently, multiagent chemotherapy has been shown to improve the survival of patients with metastatic disease, and this has started a paradigm shift in the management of patients with localized pancreatic cancer. Tsai et al describe in wonderful detail this paradigm shift and provide a framework for how to approach a patient with localized pancreatic adenocarcinoma.

Trends in utilization of neoadjuvant therapy and short-term outcomes in resected pancreatic cancer

BackgroundSurgical resection and chemotherapy offer the only chance of long-term survival for pancreatic cancer. Neoadjuvant therapy (NAT) is increasingly used to optimize outcomes. Trends in NAT utilization and short-term outcomes in resected pancreatic cancer were evaluated. MethodsThe National Cancer Database (2003 to 2011) was analyzed for pancreatic cancer patients who underwent surgery ± NAT, evaluating utilization, 30- and 90-day mortality, hospital readmissions, and length of stay (LOS). ResultsAbout 16,007 underwent initial surgery and 1,736 received NAT. Over the past decade, initial surgery and multimodality NAT have steadily decreased, whereas the use of neoadjuvant radiation has remained low and the use of neoadjuvant chemotherapy (neoCT) has steadily increased. Thirty- and 90-day mortality rates and hospital readmissions were significantly higher for NAT vs initial surgery on univariate analysis. There was no significant difference in LOS or readmission rate. On multivariate analysis, neoCT had no significant impact on odds of mortality at 30 and 90 days (hazard ratio = .68, P = .285, hazard ratio = 1.32, P = .161, respectively). Advanced age, greater comorbidities, greater clinical stage disease, and resection with pancreaticoduodenectomy or total pancreatectomy negatively impacted 30- and 90-day mortality. ConclusionThe use of neoCT has increased over the past decade and does not appear to adversely affect short-term outcomes, including 30- and 90-day mortality, LOS, and readmission rates.