Frequent Site Of Relapse Research Articles

Postoperative Radiotherapy and the Role of Regional Lymph Node Irradiation in Localized Merkel Cell Carcinoma: A Single-Center Retrospective Analysis.

The aim of this study was to analyze the pattern of relapse of patients with Merkel cell carcinoma (MCC) that underwent resection of the primary tumor site and postoperative radiotherapy at the Department of Radiation Oncology of Heidelberg University and to determine the role of the elective radiotherapy of regional lymph nodes with respect to SLNB results. A total of 57 patients were included in the present retrospective analysis. A total of 33 patients had additional lymph node irradiation (LNI); 24 had postoperative radiotherapy of the tumor bed only. Median follow-up was 43 months. Recurrence rate of the total cohort was 22.8%. Most relapses (69%) occurred in the regional nodes. Cumulative infield-tumor recurrence rate was low with 5.3%. Regional recurrence was more frequent in the cohort without LNI with 85.7% versus 37.5% with LNI. These results were similar for patients with negative sentinel lymph node (SLN) only with 80% regional relapses for those without LNI versus 33% with LNI. In conclusion, our data show that regional recurrence is the most frequent site of relapse in stage I-III MCC treated with curative intended postoperative radiotherapy and that elective irradiation of the regional lymph nodes reduces the risk of regional relapse even if the SLN was negative.

Survival outcome of pulmonary metastasectomy among the patients with colorectal cancers.

Pulmonary metastasectomy for the treatment of metastatic colorectal cancer is essential, but high ranked evidence of survival benefit is lacking. Here, we aimed to examine the prognostic factors after pulmonary metastasectomy in patients with colorectal cancer. This is a single-center, retrospective hospital-based observational case series study. We reviewed data for 607 patients with metastatic colorectal cancer (mCRC) who were treated and observed from 2012 to 2019. Of the 607 patients with mCRC, 87 were with solitary lung metastases. Of the 87 patients, 39 were not appropriate for metastasectomy, while 15 patients recognized as suitable candidates by the multidisciplinary thoracic tumor board rejected metastasectomy. Consequently, only 33 patients were included in the final analysis. Rectum was detected as the primary site in 16 (48.5%) patients. Over 80% of patients had metachronous lung metastases, with a median of 29.0 months from initial diagnosis. Video-assisted thoracic surgery with wedge resection was performed in 20 (60.6%) patients. Over 90% of patients had solitary metastasis resected, with 97% of R0 resection. Median tumor size was 23.0 mm (min: 10; max: 90). Adjuvant treatment was given to 31 (93.9%) patients, while neoadjuvant treatment was given only to 8 (25%) patients. Of the 33 patients, there were 25 (75.7%) relapses. The most frequent site of relapse was lung in 15 (45.5%) patients. Interestingly, there were only 4 (12.2%) patients who had a relapse in the liver after lung metastasectomy. We found that median disease-free survival (DFS) and overall survival (OS) were 43.0 (13.0-73.0) and 55.0 (31.6-78.4) months, respectively. Pulmonary metastasectomy was associated with significantly long-time survival rates in mCRC (43 months of DFS and 55 months of OS). The second relapse occurred in 25 (75.7%) patients, with isolated lung metastases in nearly half of the patients (45.5%). Therefore, lung metastases in mCRC were unique and a multidisciplinary team including a thoracic surgeon should manage these patients.

Pattern of local recurrence after mastectomy and reconstruction in breast cancer patients: a systematic review.

This study aimed to describe the locations of local recurrences based on the mastectomy and reconstruction type in breast cancer patients. In November 2020, a systematic literature review was performed through MEDLINE/PubMed and the Cochrane Centre Register of Controlled Trials. Publications that included skin-sparing or nipple-sparing mastectomy followed by breast reconstruction and described the location of local recurrences were analyzed. Exclusion criteria included salvage or prophylactic mastectomy, unclear distinction between local and regional recurrences, rare tumor types. From 19 publications, 272 local recurrences lesions were reported in a total of 4,787 patients. After autologous reconstruction (n=2,465), local recurrences were located in the skin in 45 (1.8%) patients, in the chest wall in 18 (0.7%), and in the nipple-areolar complex in 9 (0.4%). After implant reconstruction (n=1,917), local recurrences sites included the skin in 91 (4.7%) patients, chest wall in 8 (0.4%), and nipple-areolar complex in 8 (0.4%). Of the 70 lesions with reported in-breast location, 57 (81.4%) relapsed in the original tumor location. Although meta-analysis was not conducted, present analysis demonstrated that most local recurrences after skin-sparing or nipple-sparing mastectomy occurred within the skin or subcutaneous tissues. It was found that the original tumor location was the most frequent site of relapse. Therefore, special attention should be paid to the original tumor overlying the skin while planning postmastectomy radiation therapy.

Clear cell sarcoma of the kidney in Austrian children: Long-term survival after relapse.

Clear cell sarcoma of the kidney (CCSK) is a rare malignant childhood renal tumour. Recently, the central nervous system (CNS) was found to be the most frequent site of relapse associated with a poor outcome. Optimal treatment strategies are scarce. Retrospective data analysis of all Austrian children with CCSK. They were enrolled in the Austrian-Hungarian Wilms Tumour Study (AHWTS) 1989, the SIOP93-01 or the SIOP2001 study between 1990 and 2019. Demographic, diagnostic, treatment-related variables and survival data were analysed. We identified 12 children with CCSK (M=7, F=5; median age 1.6years). All had localised disease (stage I: 2; stage II: 2; stage III: 8) at diagnosis, and a first complete remission (CR1) was achieved in 12/12. Six patients are in an ongoing CR1 (median follow-up 10years). Six other patients had a relapse (local 1; brain 5) a median time of 2.4years from diagnosis. Two patients died of the disease 4months and 2.8years after first relapse. Four of five patients with CNS relapse are in CR2 with a median follow-up time of 9.3years after relapse diagnosis. Relapse treatment included a combination of chemotherapy, radiation and surgery. Two children received high-dose chemotherapy followed by autologous stem cell rescue, and one child received intrathecal mafosphamide. Long-term side effects after treatment were impaired tubular renal function (n=4), cardiomyopathy (n=1) and growth disorders (n=1). In this series, the brain was the most common site of relapse. Long-term survival after recurrence was achievable with intensive multimodal therapy.

Systematic Review of the Burden and Treatment Patterns of Adult and Adolescent Acute Lymphoblastic Leukemia in India: Comprehending the Challenges in an Emerging Economy

BackgroundIn the present systematic literature review, we sought to describe the burden and treatment practices of adult acute lymphoblastic leukemia (ALL) in India, which reflect the realities and outcomes in a middle-income country. Materials and MethodsWe conducted a search for reported studies using terms such as “adult ALL,” “epidemiology,” and “treatment” in the Medline, Embase, Cochrane, and other database sources. We obtained 249 articles and 18 conference abstracts reported until December 2019. A total of 40 studies were selected to qualitatively summarize the data. ResultsThe proportion of ALL among adult patients diagnosed with acute leukemia at reporting institutions from 16 Indian studies ranged from 7.3% to 57.8%. Most studies were performed in Northern India (n = 12), had a male preponderance (range, 57%-80%), and had a predominance of B-ALL (range, 65.2%-75.9%). The treatment protocols used for ALL included MCP-841, BFM (Berlin-Frankfurt-Münster)-90, chemotherapy plus a tyrosine kinase inhibitor, GMALL (German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia), and hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone). The complete remission rates and median overall survival for these protocols ranged from 46.7% to 91.4% and 7 to 46 months, respectively. The overall relapse rates were 24.3% to 57.1% within median time of 9 to 24 months, with bone marrow the most frequent relapse site. After relapse, most patients had chosen palliative therapy (range, 78.7%-96.0%). The major treatment-related toxicities included neutropenia, myelosuppression, and infection. ConclusionsThe results from Indian studies on adult ALL are heterogeneous, reporting a diverse incidence and poor overall outcomes using varied non-contemporaneous treatment protocols adapted from the developed world. A comprehensive countrywide approach to diagnosis, treatment, and follow-up and the potential incorporation of novel therapies could improve the prognosis and outcomes of adult ALL in India.

Early-stage KRAS G12C-mutated non-small cell lung cancer (NSCLC) in Australia.

e21053 Background: KRAS is frequently mutated in NSCLC, especially in Caucasian populations. Until recently there have not been effective targeted therapies against KRAS but the recent advent of active agents has thrown a spotlight on this disease. Methods: A database of NSCLC cases undergoing lobectomy or pneumonectomy with curative intent at Austin Health, Victoria, Australia was examined. Analysis for KRAS mutations was carried out using the LungCarta panel. Results: Four hundred and fifty nine cases underwent mutation analysis and 203/459 (44%) were wild type. KRAS mutations were identified in 100/459 cases (21.8%), including 3 cases where the specific mutation was not specified. KRAS G12C cases comprised 40/97 (8.5% of all cases, 41% of specified mutation KRAS cases) and other KRAS mutations comprised 57/97 (59%) - most commonly G12V (25 cases) and G12D (13 cases). Additional mutations were identified in 14/40 (36%) G12C mutation cases (10 dual and 4 triple – most commonly TP53 9, STK11 3 and PIC3CA 2). In non-G12C cases, multiple mutations were identified in 24% of cases. Considering the 40 G12C cases, histology was squamous cell in 21 cases, adenocarcinoma 13 and other 5. Males comprised 21/40 cases, median age at diagnosis was 61 year (range 34 – 78), with stage I 22 cases, stage II 12; stage IIIA 5 and one stage 4 (solitary brain metastasis). Thirty six patients (90%) had smoked tobacco with median exposure of 44 pack years (range 13-100) including 18 ex-smokers who had ceased a median 9 years (range 1 - 28) prior to the diagnosis of lung cancer. PD-L1 expression was analysed using the 28-8 antibody. For the 38 cases analysed, PD-L1 expression was ≥ 50% in 6 (16%), ≥ 5% in 12 (32%) and < 1% in 24 (63%). The estimated median overall survival was 4.9 years with 27% 10 year survival. Twenty three patients (58%) died from the index lung cancer, 8 (20%) remain alive and 9 (23%) died of other causes: 4 from a 2nd lung cancer, 4 from a non-lung cancer and one from liver failure. Data on sites of recurrence were available for 16 of the 23 cases who died from the index lung cancer, with initial recurrence sites being lung/local 7 patients, brain 6, bone 2, liver 1. A total of 9 patients (56%) developed brain metastases at some time. Conclusions: KRAS G12C is a common subgroup of NSCLC in the Australian population and almost all of cases were tobacco smokers. Additional mutations were identified in over a third of cases. Locally recurrent disease or brain metastases are the most frequent sites of relapse and over half of patients with recurrent disease develop brain metastases.

PD18-02 THE EFFECTIVENESS OF TEMPLATE-BASED REGIONAL LYMPH NODE DISSECTION IN REDUCING LOCOREGIONAL RECURRENCE IN PATIENTS WITH CLINICALLY NODE-NEGATIVE UPPER URINARY TRACT UROTHELIAL CARCINOMA

You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma I (PD18)1 Apr 2020PD18-02 THE EFFECTIVENESS OF TEMPLATE-BASED REGIONAL LYMPH NODE DISSECTION IN REDUCING LOCOREGIONAL RECURRENCE IN PATIENTS WITH CLINICALLY NODE-NEGATIVE UPPER URINARY TRACT UROTHELIAL CARCINOMA Ryuji Matsumoto*, Takashige Abe, Noritaka Takada, Keita Minami, Toru Harabayashi, Satoru Maruyama, Hiroshi Kikuchi, Takahiro Osawa, and Nobuo Shinohara Ryuji Matsumoto*Ryuji Matsumoto* More articles by this author , Takashige AbeTakashige Abe More articles by this author , Noritaka TakadaNoritaka Takada More articles by this author , Keita MinamiKeita Minami More articles by this author , Toru HarabayashiToru Harabayashi More articles by this author , Satoru MaruyamaSatoru Maruyama More articles by this author , Hiroshi KikuchiHiroshi Kikuchi More articles by this author , Takahiro OsawaTakahiro Osawa More articles by this author , and Nobuo ShinoharaNobuo Shinohara More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000861.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The role of lymph node dissection (LND) for the management of patients (pts) with nonmetastatic upper urinary tract urothelial carcinoma (UTUC) remains controversial. Therefore LND was easily skipped based on surgeons’ preference, although locoregional recurrence was known to be the most frequent relapse site. This study aimed to investigate the recurrence patterns following a radical nephroureterectomy plus template-based regional LND in pts with clinically node-negative UTUC. METHODS: A total of 105 pts with cTa-3N0M0 upper UTUC were analyzed. All of them underwent regional LND during the laparoscopic nephroureterectomy in accordance with a previously reported anatomical template-based rule [Abe et al., J Endourol 2015]. During follow-up, pts underwent lung and abdominal computed tomography at 3- or 6-month intervals, and potential recurrent nonurothelial sites were identified. The Kaplan–Meier method was used to estimate the nonurothelial recurrence-free survival (RFS) and cancer-specific survival (CSS). Locoregional recurrence was defined as a relapse within the retroperitoneal area of the removed tumor and regional lymph nodes. Micro-metastasis was evaluated by pan-cytokeratin immunohistochemistory (IHC). RESULTS: The median age was 72 years (interquartile range, 65-78) and 71% of the pts were men. The pT stage distribution was pTa-is in 18, pT1 in 29, pT2 in 40, pT3 in 15 and pT4 in 3. The median number of lymph nodes removed was 12 (range: 1–59), and 7 out of 105 (6.7%) patients had lymph node metastases. IHC detected additional 5 pts with micro-metastasis in the removed lymph nodes. The median follow-up time was 60 (interquartile range: 30–85) months. The 5-year nonurothelial RFS and CSS rates in all pts were 79.3% and 85.6%, respectively. Non-urothelial disease recurrence was observed in 21 (20%) patients at a median of 10 (range: 1–33) months after a radical nephroureterectomy. Locoregional recurrence, distant metastasis, and both were observed in 5 (4.8%), 15 (14.3%), and 1 (0.9%) patients, respectively. The predominant sites of distant metastasis were lung (n = 7), distant node (n = 5), liver (n = 3), and bone (n = 2). CONCLUSIONS: This study confirmed that with template-based LND, the number of pts with locoregional recurrence was smaller than those with distant metastasis in contrast to the previous studies. Our observation strongly suggests that regional LND may promote local disease control, eliminating micro-metastasis in pts with clinically node-negative UTUC. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e375-e376 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ryuji Matsumoto* More articles by this author Takashige Abe More articles by this author Noritaka Takada More articles by this author Keita Minami More articles by this author Toru Harabayashi More articles by this author Satoru Maruyama More articles by this author Hiroshi Kikuchi More articles by this author Takahiro Osawa More articles by this author Nobuo Shinohara More articles by this author Expand All Advertisement PDF downloadLoading ...

The role of brigatinib in crizotinib-resistant non-small cell lung cancer.

Despite the advances in new targeted therapies in ALK positive population, most patients progress under ALK inhibitors within first 2 years; being the brain the most frequent site of relapse. ALK mutations, in ~30% of patients, are the main known mechanism of resistance. Classically, second-generation ALK inhibitors have been the standard of care in the crizotinib-resistant population; however, each ALK inhibitor has a different spectrum of sensitivity to ALK mutations, complicating the optimal treatment strategy for the resistant population. Brigatinib (AP26113) is a novel highly selective and potent inhibitor of ALK and ROS1 with a high degree of selectivity. In vitro, brigatinib not only inhibited ALK with 12-fold higher potency compared to crizotinib, but also inhibited IGF-1R, FLT3 and EGFR mutants, with some activity against the EGFRT790M resistance mutation. In xenograft models, brigatinib overcomes resistance to ALK inhibitors, including the ALK G1202R mutation, which is resistant to first- and second-generation inhibitors. The efficacy of brigatinib in crizotinib-resistant, ALK-positive patients has been demonstrated in two early studies, which led to its approval in this setting, and it is currently being investigated as the first-line therapy versus crizotinib in tyrosine kinase inhibitor-naïve patients. Brigatinib demonstrates not only promising whole-body activity, but also an impressive improvement of intracranial outcomes in terms of both objective response rate and progression-free survival in the crizotinib-resistant population, with optimal efficacy at 180 mg (following a 90 mg run-in for 7 days) and good tolerance. These data confirm brigatinib as an excellent therapeutic strategy after crizotinib failure, particularly in the setting of central nervous system involvement. In this review, we summarize the two main clinical studies reported to date with brigatinib in ALK-positive advanced NSCLC patients, in particular, in the crizotinib-resistant population. We also address the mechanism of action for development of resistance and the challenging issues of optimal implementation for sequences of administration for ALK inhibitors.

Relapse of childhood acute lymphoblastic leukemia and outcomes at a reference center in Latin America: organomegaly at diagnosis is a significant clinical predictor

ABSTRACTObjective: Relapse is the major cause of treatment failure in acute lymphoblastic leukemia (ALL) of childhood; it is more frequent among high-risk patients from low-middle income than from high-income countries. The frequency, sites and outcome of relapsed ALL in children of northeast Mexico over a decade was documented.Methods: A retrospective analysis of 246 children belonging to a low-income group <16 years with de novo ALL during 2004–2015 was performed. Five-year overall survival (OS) and event-free survival was estimated by Kaplan–Meier analysis. Data on time, site, response to therapy and final outcome of relapse were analyzed. Hazard ratios (HRs) of relapse and death were estimated by the Cox regression model. Very early relapse was defined as that occurring in <18 months, early relapse between 18 and 36 months, and late relapse >36 months from diagnosis, respectively.Results: Eighty-seven (35.4%) children relapsed. Five-year OS was 82.6% in children without relapse vs. 42% for relapsed patients. Bone marrow (BM) was the most frequent site of relapse (51.72%). Isolated central nervous system (CNS) relapses occurred in 29.9%. Five-year OS was 11.2% for BM and 15.5% for early relapse. HR of relapse for organomegaly was 3.683, 2.247 for an initial white blood cell count >50 000 × 109/l and 1.169 for positive minimal residual disease status.Conclusion: A high rate of very early, CNS, and BM relapse with a considerably low 5-year OS requiring reassessment of therapy was documented. Organomegaly at diagnosis was a highly significant clinical predictor for relapse.

Real-world outcomes of treatment for acute lymphoblastic leukemia during adolescence in a financially restricted environment: Results at a single center in Latin America.

There is a paucity of the studies of adolescents with acute lymphoblastic leukemia (ALL). This is more noticeable in low- and middle-income countries. The international 5-year event-free survival (EFS) and overall survival (OS) for this age group is around 80%, with pediatric-inspired protocols offering better results. A retrospective analysis of adolescents aged 16-20 diagnosed with ALL during the period 2004-2015 treated with a high-risk pediatric protocol at an academic center from a middle-income country was performed. Five-year OS and EFS were estimated by the Kaplan-Meier analysis. Hazard ratios of relapse and death were estimated by the Cox regression model. Five-year EFS and OS for 57 adolescents were 23.3% and 48.9%, respectively. From the 41 patients who achieved complete remission, 24 (58.5%) relapsed. Bone marrow and central nervous system were the most frequent sites of relapse. Hazard ratio of treatment failure and death for patients with organomegaly at diagnosis was 2.026 and 2.970, respectively. Treatment-related toxicity developed in 31 (54.4%) patients and febrile neutropenia was the most frequent in 14 (24.6%) cases. Twelve patients (21.1%) had poor adherence to treatment. High relapse rate and low 5-year EFS compared with international standards, was documented. Use of intensified pediatric regimens, adherence to proven effective medications, improved supportive care, and prevention of abandonment are necessary to improve survival rates in these patients.

Survival Rates of Adults With Acute Lymphoblastic Leukemia in a Low-Income Population: A Decade of Experience at a Single Institution in Mexico.

The therapeutic progress for adults with acute lymphoblastic leukemia (ALL) has been slow, with a 5-year survival of 30% to 45% in developed countries. Scarce information is available regarding the treatment and survival rates from nonindustrialized populations. In the present study, the characteristics of adults with ALL at a single institution were documented. The clinical files of patients aged≥ 18 years who had been diagnosed with ALL from 2005 to 2015 at a reference center in Mexico were scrutinized. Overall survival (OS) and event-free survival (EFS) were determined using the Kaplan-Meier method. The hazard ratios for death and relapse were estimated using Cox regression analysis. A total of 94 adults were included. Their median age was 33 years; 69 (73.4%) had high-risk and 25 (26.6%) had standard-risk ALL. Of the 94 patients, 67 (71.3%) achieved complete remission (CR), 20 (21.3%) experienced disease resistance, and 7 (7.4%) died early during induction to remission, mainly of sepsis. The 5-year EFS and OS was 23.4% and 31.1% for the whole group and 24.9% and 38.9% for patients who achieved CR, respectively. Of the 94 patients, 50 (43.9%) died of sepsis or disease progression. Relapse developed in 43 patients (45.7%). The median survival after relapse was 6.93 months. Bone marrow was the most frequent site of relapse (21 patients [48.8%]) and conferred a significantly lower 5-year OS of 16.4%. Adults with ALL in Mexico had high-risk characteristics and an increased relapse rate; however, the OS after CR was similar to the greatest achieved in developed countries, suggesting that a threshold for curing adult ALL with current therapeutic strategies has been reached.

Extramedullary relapse in lumbar spine of a patient with acute promyelocytic leukemia after remission for 16 years: case report and literature review

A 46-years female patients with extramedullary relapse of lumbar spine after 16-year remission of acute promyelocytic leukemia (APL) was reported. After surgical treatment, local radiotherapy combined with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), the patient achieved and maintained a second complete remission (CR). The literature showed that extramedullary relapse was a relatively rare complication of APL. The recurrence time of APL after remission varied from 6 months to 12 years, and the central nervous system was the most frequent site of relapse. The causes and treatment for extramedullary relapse of APL are various. The successful diagnosis and treatment of this case may provide experience for management of extramedullary relapse in APL patients. Key words: Leukemia, myelocgtic, acute; Recurrence

Adjuvant chemotherapy for resected colorectal cancer metastases: Literature review and meta-analysis.

Surgical resection is the only option of cure for patients with metastatic colorectal cancer (CRC). However, the risk of recurrence within 18 mo after metastasectomy is around 75% and the liver is the most frequent site of relapse. The current international guidelines recommend an adjuvant therapy after surgical resection of CRC metastases despite the lower level of evidence (based on the quality of studies in this setting). However, there is still no standard treatment and the effective role of an adjuvant therapy remains controversial. The aim of this review is to report the state-of-art of systemic chemotherapy and regional chemotherapy with hepatic arterial infusion in the management of patients after resection of metastases from CRC, with a literature review and meta-analysis of the relevant randomized controlled trials.

Features, risk factors and clinical outcome of "very late" recurrences after surgery for localized renal carcinoma: A retrospective evaluation of a cohort with a minimum of 10 years of follow up.

To evaluate the features and the predictors of "very late" recurrences after surgery for localized renal cell carcinoma. Since 1983, an institutional database with data of more than 2300 consecutive patients treated for renal cancer has been prospectively maintained. Patients N0 /Nx M0 followed for a minimum of 10 years without recurrences were retrieved. The site, time and treatment of recurrences observed afterwards were recorded, and the predictors were investigated by Cox regression analysis. A total of 554 patients (231 women, 323 men; age 59.3 ± 11.6 years) followed for a mean/median time of 15.1/13.6 years (range 10.0-34.1 years) were analyzed. A recurrence was observed in 26 patients (4.6%) after a mean/median interval of 13.3/12.3 years (range 10.5-30.2 years). The pathological stage 2/3 was the only independent predictor of recurrence (P = 0.003), and it was related also to the latency of recurrence (mean/median latency 15.4/14.0, 11.4/10.8 and 12.5/12.0 years, respectively, for stage 1, 2 and 3; P < 0.005 for stage 1 vs stage 2 or 3). The contralateral kidney was the most frequent site of relapse in patients with stage pT1, whereas multiple sites were more frequent for stage pT2 and pT3. The risk of a "very late" recurrence of renal cancer is approximately 5%, and it depends on the pathological stage. For stage pT1, the kidney/s should be surveilled for indefinite time, preferably by ultrasound to reduce the X-ray exposition; for stage pT2 and pT3, the abdomen and the lungs should be monitored, by computed tomography scan during the first years, and then by abdominal ultrasound and chest X-ray.

Management of nodal recurrences of endometrial cancer with IMRT

ObjectivePelvic and paraortic lymph nodal regions are frequent sites of relapse in women with endometrial cancer who have not undergone adjuvant external beam radiation. We investigated outcomes after definitive management of nodal relapses of endometrial cancer with intensity modulated radiation therapy (IMRT). MethodsBetween 2002–2012, 38 patients with endometrial cancer who had no prior external beam radiation were treated definitively using IMRT for regionally confined pelvic or paraortic nodal recurrences. Thirteen (34%) had chemotherapy prior to radiation, and 21 (55%) received concurrent chemotherapy. The nodal basins were typically treated to 45–50Gy, with a boost to the gross tumor to a median total of 64.7Gy (range 59–73Gy). ResultsThe median overall survival from date of recurrence was 46.1months and the 2-year survival was 71%. Patients who received concurrent chemotherapy had a significantly longer median survival (61.9months versus 28.7months, p=0.034). In-field failures were more frequent in patients who received chemotherapy prior to radiation, had a shorter recurrence-free interval, received a lower radiation dose, and had higher tumor grade. Three patients (8%) experienced grade 3–4 late gastrointestinal (GI) toxicity. ConclusionsLong-term survival can be achieved in women with nodal recurrences of endometrial cancer. The use of concurrent chemotherapy and dose escalation with IMRT as feasible may improve survival for women with isolated nodal recurrences of endometrial cancer.

Secondary Cytoreduction in Platinum-Resistant Recurrent Ovarian Cancer: A Single-Institution Experience

The purpose of this study was to observe the role of secondary cytoreductive surgery in platinum-resistant recurrent ovarian cancer (OC) patients. We collected data of patients affected by recurrent OC treated between 1995 and 2013. Inclusion criteria were: invasive epithelial OC histologically documented, cytoreductive surgery and platinum-based chemotherapy at first-line treatment with evidence of complete response to treatment, disease-free interval <6 months, and no concomitant neoplasia. Patients considered susceptible of cytoreductive surgery (group A) were compared with a historical series of patients with similar characteristics but not eligible for surgery (group B). Of 122 platinum-resistant patients, 18 met the inclusion criteria for the study and were enrolled. They were compared with a historical series of 18 patients not surgically treated with analogous clinical and pathological features. The most frequent sites of relapse included pelvic and aortic lymph nodes (39 %), peritoneum (33 %), bowel (28 %), and pelvis (22 %). A low rate of intraoperative and postoperative complications was reported. No deaths were recorded. Overall survival was significantly longer in cytoreductive group when compared with the control group (P = 0.035). Median overall survival was 44 months. Estimated 5-year overall survival rates were 57 versus 23.5 % for groups A and B, respectively. Surgery could represent a useful adjunct to chemotherapy in the management of platinum-resistant recurrent OC patients, carefully selected, in highly selected centers. Larger prospective trials are needed to further confirm our experience.

712P - A Three-Step Strategy of Induction Chemotherapy, Chemo-Radiotherapy and Surgery in Locally Advanced Pancreatic Cancer (Lapc) Patients. Role of a Nonlinear Mixed Effects Modeling to Predict Outcome

ABSTRACT Aim: The optimal strategy for patients with LAPC remain a therapeutic challenge. A growing evidence suggests that both, pts with borderline resectable and unresectable tumors may benefit from a multimodal approach aimed at improving resectability and survival times. In the present work our experience after a long-term follow-up period is reported. Methods: From December 2005 to July 2011, 67 histologically confirmed LAPC, endoscopic ultrasound (EUS) staged T3-4 and/or N+ were retrospectively analysed. They received induction gemcitabine/oxaliplatin- based chemotherapy followed, in case of radiological response or stable disease, by chemo-radiotherapy (50.4 Gy concurrently with daily capecitabine and weekly oxaliplatin). Salvage surgery was performed when technically feasible. We have applied a nonlinear mixed effects (NLME) modeling to evaluate the impact of dynamic changes in tumor size, Ca- 19.9, neutrophil-lymphocyte ratio and platelet-lymphocyte ratio on the clinical outcome of these patients. Results: The median age was 63 years (range 35-85). Male to female 36/31. Thirty eight pts (57%) completed the whole program (group A), whereas 27 (40%) received chemo and radioterapy but were not elegible for surgery (Group B). Two pts (3%) progressed after induction chemotherapy (Group C). EUS staged T4 or N+ was found in 20 (30%) and 24 (36%) respectively. Toxicity profile was mild, with no grade 4 toxicity being documented. On an intent to treat basis, R0 resection rate was 57%; ypT0ypN0 were observed in 11 (29%) of patients. Among resected patients, local and distant failure rates were 5% and 55%, respectively. The liver was the most frequent site of relapse 21(43%) pts. After a median follow up of 23 months (range 4 to 102), median PFS was 21, 10 and 1 month in groups A, B and C respectively (p = Conclusions: Our date suggest that this three-step strategy is feasible and active in LAPC patients. The NMLE population modeling will be presented at the meeting Disclosure: All authors have declared no conflicts of interest.

The Central Nervous System as a Sanctuary Site in ALK-Positive Non–Small-Cell Lung Cancer

Anaplastic lymphoma kinase (ALK) gene rearrangements define a distinct molecular subset of non-small-cell lung cancer that is highly responsive to treatment with the ALK inhibitor crizotinib. Recently, it has been recognized that the brain is a frequent site of relapse among ALK-positive patients treated with crizotinib. In this report, we expand on these observations and present a series of ALK-positive patients with two distinct forms of metastatic, central nervous system involvement: intramedullary spinal cord metastasis and leptomeningeal carcinomatosis.

Abdominal scar recurrence of squamous cell carcinoma of cervix following simple hysterectomy.

Carcinomas of uterine cervix recur most commonly locoregionally after surgery and/or radiation therapy. The pelvis (parametrium or lymph nodes) and vagina are the most frequent sites of relapse. Distant metastases are rare, and usually observed in the lungs, bone, and liver [1]. On the other hand, the common primary sites of patients with skin metastases are the breast, large intestine, lung, and ovary. However, the incidence of incisional skin metastases from carcinoma cervix is extremely rare; incidence ranges from 0.1 to 0.2 % [2]. The present case is unusual because incisional skin metastasis was seen in squamous cell carcinoma cervix where patient did not receive any adjuvant treatment after simple abdominal hysterectomy and presented to us 2.5 years after surgery with skin and omental metastases.

Incidence and outcomes of patients with late recurrence of Wilms' tumor

Most relapses from Wilms' tumor occur within 2 years from diagnosis. This study aims to describe the incidence and outcome of patients who experienced a late recurrence (LR) more than 5 years after diagnosis across several clinical trials, and to develop evidence-based recommendations for follow-up surveillance. Available records on children with Wilms' tumor enrolled onto 10 national or international cooperative clinical trials were reviewed to identify patients who experienced a LR. Seventy of 13,330 (0.5%) patients with Wilms' tumor experienced a LR. No gender bias was observed. Median time elapsing between initial Wilms' tumor diagnosis and first recurrence was 13.2 years (range: 5.1-17.3 years). Initial tumor stage was: stage I (15); stage II (19); stage III (14); stage IV (8); bilateral disease stage V (14). The most frequent sites of relapse were--abdomen: 21, lungs: 20, and contralateral kidney: 15. Thirty-five children died of disease progression. Recurrence in the contralateral kidney was associated with a better outcome (13/15 patients alive), while initial tumor stage did not seem to influence the post-recurrence outcome. Therapies administered at recurrence varied between centers, preventing any conclusion about the best salvage treatment. LR of Wilms' tumor is rare and associated with similar outcome to those experiencing earlier recurrence. The low rate of LR does not justify prolonged monitoring. Further study of the biology of these tumors may give us some insights in regards to mechanisms on tumor cell dormancy or cancer stem cell maintenance.