stage-IV Disease Research Articles

A Clinical Review of the Co-Occurrence of Myeloproliferative and Lymphoproliferative Neoplasms

The co-occurrence of myeloproliferative (MPN) and lymphoproliferative neoplasms (LPN) is rare and many publications have been limited to small case reports. Others have involved a considerable number of patients, but the coexistence remains underreported and inadequately studied. A recent retrospective review reported that a MPN patients have a 2.8-fold higher relative risk of developing LPN.A database developed at Weill Cornell Medicine (WCM) was queried for patients with ≥3 visits between 1998-2018 with a diagnostic code for a MPN and lymphoma or myeloma subtype. Patients identified were verified to ensure that study inclusion criteria were satisfied. Observed co-occurrence was compared to nation-wide reported prevalence.Demographic and clinical details of 24 patients with a MPN and LPN were recorded (Table 1). The ratio of males to females was 1.7. Essential thrombocythemia and polycythemia vera, and chronic lymphocytic leukemia (CLL) were the leading MPN and LPN subtypes, respectively. Patients were assigned to risk or staging categories at diagnosis based on subtype-specific criteria (Table 2).Median values for diagnostic bone marrow biopsy findings in 14 patients were 2% [0-5] for myeloblasts and 80% [15-100] for cellularity. Additionally, 10 patients had evaluated reticulin fibrosis: 5 (50.0%) presented as MF-0, 4 (40.0%) as MF-1, and 1 (10.0%) as MF-2.Progression to myelofibrosis was confirmed by morphology in 1 (4.2%) patient 10.1 years after a polycythemia vera diagnosis and 5.4 years after a diffuse large B-cell lymphoma (DLBCL) diagnosis. Progression to acute myeloid leukemia was confirmed by morphology in 1 (4.2%) patient 2.4 years after a chronic myelomonocytic leukemia diagnosis and 1.2 years after a smoldering myeloma (SM) diagnosis.Interphase fluorescence in situ hybridization (iFISH) detected cytogenetic abnormalities in 5/8 (62.5%) CLL patients: 2/5 (40.0%) and 5/5 (100.0%) patients harbored deletions in trisomy 12 and 13q14, respectively. Immunoglobulin heavy chain variable region gene (IGVH) status was unmutated in 2 (25.0%) patients. One (12.5%) patient was CD38+ and 2/6 (33.0%) patients were ZAP-70+. At diagnosis, all 8 patients presented with early stage disease (Rai stage 0-II). Based on the CLL-specific international prognostic index (IPI), 3/8 (37.5%) and 5/8 (62.5%) presented as low-risk and intermediate-risk, respectively.Of the 6 lymphoma patients: 5 (83.0%) patients presented with Ann Arbor stage-IV disease at diagnosis. Four (66.7%) patients presented as low/intermediate-risk, and 2 (33.3%) presented as high-risk based on disease-specific IPIs. One patient presented with -17p by iFISH. All 4 patients that were evaluated for Ki-67 had moderate/high expression.Of the 7 multiple myeloma (MM) patients, 6 (85.7%) presented as stage 1 and 1 (14.3%) as stage 3. Of the 3 SM patients, all 3 presented as low risk [12]. In addition, these patients were categorized as IgG-K (4; 40.0%), IgG-L (2; 20.0%), IgA-K (1; 10.0%), IgA-L (1; 10.0%), IgM (1; 10.0%), and biclonal IgG-L/IgA-L (1; 10.0%) [13].Mutation statuses were identified by commercially tested myeloid or lymphoid molecular panels. As expected in this MPN subtype distribution, 11 (45.8%) are JAK2+, 2 (8.3%) are MPL+, 1 (4.2%) is BCR-ABL+, and 1 (4.2%) is CALR+ (Table 3).The risk of a co-occurrent MPN and LPN is higher than expected if they are mutually exclusive (Table 4A-4B, 5). Of interest, 13 (54.2%) patients were diagnosed with a MPN 11.8±18.8 years prior to a LPN; conversely, 11 (45.9%) were diagnosed with a LPN 6.5±6.2 years prior to a MPN. In addition, MPN therapy was started 2.0±2.3 years after a MPN diagnosis, and LPN therapy was started 2.6±4.0 years after a LPN diagnosis. A review of survival analysis requires larger subtype populations since the degree of survival can vary greatly, but it has been reported that patients with a MPN or LPN have significantly reduced life expectancy when compared to the general population. Median follow-up for our patient is 8.2 years (1.5-28.0) with 17/24 (70.8%) patients still being actively followed at our institution, 6 (25.0%) are been lost to follow-up, and 1 (4.2%) is deceased.The significant prevalence of these hematologic malignancies in combination emphasizes the importance of performing a bone marrow biopsy, which we espouse at our institution, cytogenetic analysis, and myeloid and lymphoid molecular testing to identify mutations. [Display omitted] DisclosuresFurman:Loxo Oncology: Consultancy; Gilead: Consultancy; Verastem: Consultancy; Acerta: Consultancy, Research Funding; TG Therapeutics: Consultancy; Incyte: Consultancy, Other: DSMB; Pharmacyclics LLC, an AbbVie Company: Consultancy; Genentech: Consultancy; Sunesis: Consultancy; Janssen: Consultancy; AbbVie: Consultancy. Niesvizky:Amgen Inc.: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Ritchie:Bristol-Myers Squibb: Research Funding; Novartis: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Astellas Pharma: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau; Pfizer: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; ARIAD Pharmaceuticals: Speakers Bureau.

P15 Prevalence of EML4- ALK Fusion Gene in Adenocarcinoma Lung Patients by Using Immuno Histo Chemistry

An oral ATP- competitive TKI of ALK and c- MET, Crizotinib has shown impressive clinical activity in advanced non–small cell lung cancers especially in the tumors harboring ALK rearrangements. With FISH as the mainstay for detection of ALK rearrangements, the ALK Break Apart FISH Probe Kit (Abbott Molecular, Des Plaines, IL) has become an FDA-approved companion diagnostic for targeted therapy with the ALK inhibitor crizotinib in lung cancers. The objective of this molecular epidemiological study is to estimate the prevalence of EML4-ALK fusion gene using IHC as a cost effective alternative to FISH for Indian patients with adenocarcinoma lung. Patients with NSCLC, adenocarcinoma histology, whose tumors had been tested for EML4-ALK fusion gene using IHC were considered for this study. Permission was obtained from the Ethics committee before the start of the study. Clinical characteristics and treatment details were collected from the patient’s medical records. IHC analysis was performed using a Ventana automated immunostainer (Ventana Medical Systems, Illkirch Graffenstaden, France). Detection was performed using a multimer-technology system with the UltraView Universal DAB detection kit. A total of 204 NSCLC adenocarcinoma patients were included in the study. There were 126 (61.7%) men and 78 (38.23%) women with a median age of 57 years. Of the 204 patients, 47 (23.03%) were non-smokers and 175 (85.78%) had stage-IV disease at the time of initial diagnosis. 48 (23.52%) blocks were positive for EGFR mutations whereas 156 (76.47%) were EGFR wild type. EML4-ALK fusion gene was present in 27 (13.23%) patients whereas 177 (86.76%) tumors were EML4-ALK negative. 25 out of the 27 patients with ALK positivity received Crizotinib therapy. The incidence of EML4-ALK gene fusions (13.23%) in this Indian population is four fold high than the previous reported incidences and supports the claim of several recent studies that a relatively new ALK clone, 5A4 and D5F3 from cell signaling technology (Ventana) can accurately identify ALK rearranged lung ACA as compared to FISH. The inclusion of IHC for the detection of EML4-ALK gene fusions as a low cost alternative seems warranted.

Cáncer de pulmón microcítico. Metodología y resultados preliminares del estudio SMALL CELL

IntroductionSmall cell lung cancer (SCLC) is the most aggressive histologic type of lung cancer, and accounts for approximately 10%-15% of all cases. Few studies have analyzed the effect of residential radon. Our aim is to determine the risk factors of SCLC. MethodsWe designed a multicenter, hospital-based case-control study with the participation of 11 hospitals in 4 autonomous communities. ResultsResults of the first 113 cases have been analyzed, 63 of which included residential radon measurements. Median age at diagnosis was 63 years; 11% of cases were younger than 50 years of age; 22% were women; 57% had extended disease; and 95% were smokers or former smokers. Median residential radon concentration was 128Bq/m3. Concentrations higher than 400Bq/m3 were found in 8% of cases. The only remarkable difference by gender was the percentage of never smokers, which was higher in women compared to men (P<.001). Radon concentration was higher in patients with stageIV disease (non-significant difference) and in individuals diagnosed at 63 years of age or older (P=.032). ConclusionsA high percentage of SCLC cases are diagnosed early and there is a predominance of disseminated disease at diagnosis. Residential radon seems to play an important role on the onset of this disease, with some cases having very high indoor radon concentrations.

Prognostic factors affecting outcomes in multivisceral en bloc resection for colorectal cancer

OBJECTIVES:This study sought to determine the clinical and pathological factors associated with perioperative morbidity, mortality and oncological outcomes after multivisceral en bloc resection in patients with colorectal cancer.METHODS:Between January 2009 and February 2014, 105 patients with primary colorectal cancer selected for multivisceral resection were identified from a prospective database. Clinical and pathological factors, perioperative morbidity and mortality and outcomes were obtained from medical records. Estimated local recurrence and overall survival were compared using the log-rank method, and Cox regression analysis was used to determine the independence of the studied parameters. ClinicalTrials.gov: NCT02859155.RESULTS:The median age of the patients was 60 (range 23-86) years, 66.7% were female, 80% of tumors were located in the rectum, 11.4% had stage-IV disease, and 54.3% received neoadjuvant chemoradiotherapy. The organs most frequently resected were ovaries and annexes (37%). Additionally, 30.5% of patients received abdominoperineal resection. Invasion of other organs was confirmed histologically in 53.5% of patients, and R0 resection was obtained in 72% of patients. The overall morbidity rate of patients in this study was 37.1%. Ureter resection and intraoperative blood transfusion were independently associated with an increased number of complications. The 30-day postoperative mortality rate was 1.9%. After 27 (range 5-57) months of follow-up, the mortality and local recurrence rates were 23% and 15%, respectively. Positive margins were associated with a higher recurrence rate. Positive margins, lymph node involvement, stage III/IV disease, and stage IV disease alone were associated with lower overall survival rates. On multivariate analysis, the only factor associated with reduced survival was lymph node involvement.CONCLUSIONS:Multivisceral en bloc resection for primary colorectal cancer can be performed with acceptable rates of morbidity and mortality and may lead to favorable oncological outcomes.

Clinico-radiological profile of pulmonary sarcoidosis: A study of 150 patients

Objective: The main aim of this study was to study the radiological, including radiographic and computed tomographic, histopathologic and clinical profiles in patients of pulmonary sarcoidosis. Materials and Methods: A prospective study of 150 patients suspected of having sarcoidosis was carried out with their routine chest radiographs and computed tomography scans performed followed by histopatholgical analysis of the lymph nodes. Results: Most of the patients evaluated belonged to the Stage-I sarcoidosis least number of patients were from Stage-IV disease. Conclusion: All the modalities should be combined with clinico-radiologico-pathological diagnosis of the disease to avoid inconvenience to the patient and misdiagnosis.

Molecular epidemiological study of microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene using immunohistochemistry as a cost effective alternative to fluorescence in situ hybridization for Indian patients with adenocarcinoma lung

Abstract Background: With fluorescence in situ hybridization (FISH) as the main-stay for the detection of anaplastic lymphoma kinase (ALK) rearrangements, the ALK Break Apart FISH Probe Kit has become a Food and Drug Association-approved companion diagnostic for targeted therapy with the ALK inhibitor crizotinib in lung cancers. The objective of this molecular epidemiological study was to estimate the prevalence of microtubule-associated protein-like 4-ALK (EML4-ALK) fusion gene using immunohistochemistry (IHC) as a cost effective alternative to FISH for Indian patients with nonsmall-cell cancer (NSCC)-adenocarcinoma, favor adenocarcinoma lung and NSCC- Not otherwise specified (NOS). Materials and Methods: Patients with NSCC-adenocarcinoma, favor adenocarcinoma lung, and nonsmall cell lung cancer-NOS histology were considered for this study. Permission was obtained from the Ethics Committee before the start of the study. Clinical characteristics and treatment details were collected from the patient's medical records. IHC analysis was performed using a Ventana automated immunostainer (Benchmark XT). Detection was performed using OptiView DAB Detection and Amplification Kit. Results: A total of 200 NSCC-adenocarcinoma, favour adenocarcinoma and NSCC-NOS patients were included in the study. There were 122 (61%) men and 78 (39%) women with a median age of 57 years. Of the 200 patients, 43 (21.5%) were nonsmokers and 175 (87.5%) had Stage-IV disease at the time of initial diagnosis. 48 (24%) cases were positive for epidermal growth factor receptor mutations, whereas EML4-ALK fusion gene was present in 27 (13.5%) patients. 25 of the 27 patients with ALK positivity received crizotinib therapy. Conclusions: The incidence of EML4-ALK gene fusions (13.5%) in this Indian population is four-fold high than the previous reported incidences and supports the claim of several recent studies that a relatively new ALK clone, 5A4, and D5F3 from Leica/Novocastra and cell signaling technology/Ventana, respectively can accurately identify ALK rearranged lung adenocarcinoma. The inclusion of IHC for the detection of EML4-ALK gene fusions as a low cost alternative seems justified in low resource setting.

Leonine facies (LF) and mycosis fungoides (MF): A single-center study and systematic review of the literature

Leonine facies (LF) is defined as displaying facial features similar to that of a lion with prominent convexities and furrowed creases. LF develops in a very small population of patients with cutaneous T-cell lymphoma. We aimed to study the clinicopathologic features and overall prognosis associated with LF in patients with mycosis fungoides and Sézary syndrome. We conducted a single-center retrospective study, reviewing 1338 patients with mycosis fungoides seen from 1987 to 2015 at a tertiary referral center for cutaneous T-cell lymphoma, and a systematic review of 14 patients in the literature. We identified 10 patients with mycosis fungoides who developed LF. Folliculotropism was seen in all patients with LF who had facial biopsy specimens. Radiation was a beneficial therapy. Complete remission was achieved in 1 patient and overall 5-year survival was 26%. Systematic review of 10 additional patients showed that all patients with LF, including ours, had stage-IV disease and some degree of blood involvement, but not all met criteria for Sézary syndrome. This was a retrospective study with a small sample size. LF is associated with stage-IV cutaneous T-cell lymphoma, is often accompanied by folliculotropism and blood involvement, and can be treated with local electron beam therapy.

Abstract 4101: Clinical significance of ZEB1 mRNA levels in peritoneal washing for gastric cancer

Abstract Backgrounds. ZEB1 affects cancer progression by regulating Epithelial to mesenchymal transition (EMT) in some cancers. In gastric cancer, ZEB1 expression in cancer tissue has been identified as an independent prognostic factor. We also reported on a significant correlation between ZEB1 expression and diffuse phenotype in gastric cancer, and that patients with high ZEB1 expression had significantly poorer survival than those with low expression. It was also reported that ZEB1 was an independent predictor of peritoneal dissemination in gastric cancer patients, and was expressed in disseminated cancer cells in the peritoneum in the same pattern as that seen in primary lesions. Therefore, we hypothesized that ZEB1 mRNA levels in peritoneal washing (pZEB1) in conjunction with peritoneal washing cytology might predict intraperitoneal recurrence and prognosis. Objectives. The association between pZEB1 and clinicopathological parameters, and prognosis was investigated, and the possibility of using pZEB1 as a predictive marker was explored in this study. To our knowledge, this is the first study to examine the clinical implication of pZEB1 in gastric cancer. Methods. One hundred and seven consecutive patients with gastric cancer, who underwent surgical procedures that included the collection of peritoneal washing samples at the left subphrenic area at the beginning of surgery, were enrolled. RT-PCR was performed to quantify ZEB1 mRNA levels in peritoneal washing (pZEB1). The correlation between pZEB1 and clinicopathological variables and recurrence were statistically analyzed. Results. Patients were classified into the pZEB1High group (n = 27) or the pZEB1Low group (n = 80) based on their pZEB1 expression. pZEB1 was statistically correlated with pathological T category (P = 0.03) and vessel involvement (P = 0.03). 5-year disease-specific survival was 36.4% for the pZEB1High group and 64.7% for the pZEB1Low group (P = 0.02), and disease-free survival with the exception of StageIV disease was 46.9% for the pZEB1High group and 83.0% for the pZEB1Low group (P = 0.03). When subclassified into 4 categories based on washing cytology and pZEB1, the survival was worse in the pZEB1High group than in the pZEB1Low group (CY0 group: P = 0.01; CY1 group: P = 0.13). The recurrence rate for the pZEB1High group (8/27) was significantly higher than that of the pZEB1Low group (10/80; P = 0.03). Of these 18 patients, 6 developed to lymph node metastases, 6 peritoneal metastases, 5 liver metastases, and 1 lung metastasis. However, our results failed to show the statistical correlation between pZEB1 and peritoneal dissemination and peritoneal recurrence. Conclusions. pZEB1 could be a predictive marker for poor prognosis or tumor aggressiveness in gastric cancer in the same way as ZEB1 expression does so in primary lesions. It could add valuable information to conventional peritoneal washing cytology, and thus help select candidates for more powerful chemotherapies. Citation Format: Norimitsu Yabusaki, Suguru Yamada, Toshifumi Murai, Mitsuro Kanda, Daisuke Kobayashi, Chie Tanaka, Tsutomu Fujii, Goro Nakayama, Hiroyuki Sugimoto, Masahiko Koike, Shuji Nomoto, Michitaka Fujiwara, Yasuhiro Kodera. Clinical significance of ZEB1 mRNA levels in peritoneal washing for gastric cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4101. doi:10.1158/1538-7445.AM2015-4101

Every-three-week versus dose dense weekly paclitaxel neoadjuvant chemotherapy for advanced stage ovarian, fallopian tube, and peritoneal cancers

Objectives: The aim of this study was to compare operative data, toxicity, and survival between weekly dose dense (ddT) and every 3week (q3wT) paclitaxel given with carboplatin as neoadjuvant chemotherapy (NACT) for advanced ovarian cancer. Methods: We performed a retrospective study of stage III–IV ovarian, fallopian tube, or peritoneal cancers treated with NACT followed by interval cytoreduction from January 2009 to present. Carboplatin (AUC 5-6) was given every 3 weeks with ddT (paclitaxel 80 mg/m) or q3wT (paclitaxel 175 mg/m). Chi-square, Student's t test, Kaplan– Meier method, and log-rank statistics were used. Results: Eleven women treated with ddT, and 51 women treated with NACT met inclusion criteria. There were no demographic differences. Median agewas 64. Fifty-nine percent of patients had stage IIIC and 41% stage IVdisease. Therewas nodifference inmean cycles of NACT (3.6 for ddT v. 3.8 q3wT), proportion achieving a 50% decline in CA-125 (91% of ddT v. 94% of q3wT p= 0.51), or radiologic response (100% ddT v. 72% q3wT, p = 0.12). Ten ddT women (91%) and 28 q3wT women (55%) had no gross residual disease after interval cytoreduction (OR 8.21, 95% CI 0.98–69). Mean operative time (181 min ddT v. 166 min q3wT, p = 0.46), EBL (416 cc ddT v. 358 cc q3wT, p = 0.49), and rate of postoperative complications (9% ddT v. 18% q3wT, p = 0.43) were similar. Eighty-two percent of ddT v. 51% q3wT experienced grade 1–2 anemia (p= 0.043) and 55% of ddT v. 14% of q3wT had a grade 1–2 leukopenia or neutropenia (p= 0.029). One ddT patient had grade 3 hypokalemia and one q3wT patient had grade 3 anemia. A similar number of patients in each group was treated with G-CSF (36% ddT v. 55% q3wT, p = 0.26). Median progression-free survival was 16 months for ddT v. 15 months for q3wT, (p= 0.69); overall survival has not been reached. After a median of 15 months, 9% ddT women have died and 27% are alive with the disease. After a median of 21 months, 44% q3wT women have died and 27% are alive with the disease. The remaining patients have no evidence of disease. Conclusion: ddT has similar outcomes with a trend toward increased rate of cytoreduction to no gross residual disease compared to q3wT. Future studies evaluating survival benefit and symptom control between these regimens in the NACT setting are needed.

Longo procedure (Stapled hemorrhoidopexy): Indications, results

There is now sufficient data in the literature to compare pedicularhemorroidectomy (Milligan and Morgan, Ferguson), the reference operation, to the Longo procedure (stapledhemorrhoidopexy) (SH). SH is easy to perform, is associated with less pain and allows early return to normal activities. Not withstanding a higher risk of recurrence and some degree of procidentia, the long-term level of patient satisfaction is high after SH. Strict patient selection is necessary: patients should have reversible prolapse, normal anal caliber, and absence of large tags. This procedure is not recommended for stageIV disease. In case of persistent prolapse or hemorrhoidal recurrence after SH, elastic band ligation should be preferred.

Resultados de la laringectomía total en carcinoma localmente avanzado de laringe en la era de la organopreservación

Introduction and objectivesTotal laryngectomy (TL) and postoperative radiotherapy (RT), when indicated, have proven to be effective in treating cases of locally advanced laryngeal cancer. The aim of this study was to analyse the oncological outcomes of this procedure in patients with laryngeal cancer classified T3 and T4a. MethodsWe studied 80 patients (51 T3 and 29 T4a) with primary squamous cell carcinoma of the larynx who underwent TL between 1998 and 2006. Bilateral neck dissection was performed in 54 patients, unilateral in 11, and central in 4. Twenty patients (25%) received postoperative radiotherapy. ResultsMean age was 64 years with a male predominance (97%). As for habits, 96% were smokers and 89% consumed alcohol. Lymph node metastases occurred in 44% of patients and extracapsular invasion in 37% of them. All cases had tumour-free margins. In all, 25% of patients had loco-regional recurrence and 5% developed distant metastases. The 5-year disease-specific survival was 72% and 5-year overall survival was 55%. Variables associated with decreased disease-specific survival were T4 classification (P=.068), N2-N3 classifications (P=.005), extracapsular invasion (P=.018) and stage iv disease (P=.009). On multivariate analysis, the only variable associated with decreased disease-specific survival was the presence of N2-N3 nodal metastases (P=.008). ConclusionsTL is an effective treatment for the management of patients with locally advanced laryngeal cancer. Organ preservation protocols should achieve similar oncological results to those obtained with TL.

A Phase II Trial of nab-Paclitaxel as Second-line Therapy in Patients With Advanced Pancreatic Cancer

nab-Paclitaxel has been shown to disrupt pancreatic cancer stroma and was effective in combination with gemcitabine in a phase I/II trial. This study was designed to determine the efficacy of nab-paclitaxel monotherapy in previously treated pancreatic cancer patients. In this phase II trial, patients with advanced pancreatic cancer who progressed on gemcitabine-based therapy, received nab-paclitaxel 100 mg/m over 30 minutes on days 1, 8, and 15 of a 28-day cycle. The primary endpoint was 6-month overall survival (OS). Secondary endpoints were response rate (by Response Evaluation Criteria In Solid Tumors), progression-free survival, safety, and toxicity profile. Among 19 patients treated, the median age was 61 years, 9 (47%) were male patients and 18 (95%) had stage-IV disease. The primary endpoint of the study was reached with a 6-month OS of 58% [95% confidence interval (95% CI), 33%-76%] and an estimated median OS of 7.3 months (95% CI, 2.8-15.8 mo). The median progression-free survival was 1.7 months (95% CI, 1.5-3.5 mo). One patient had a confirmed partial response and 6 (32%) had stable disease as their best response. Nonhematological toxicities were generally mild with grades 1-2 nausea, anorexia, hypocalcemia, and vomiting occurring in 63%, 47%, 37%, and 26% of patients, respectively. Grades 3-4 neutropenia, neutropenic fever, and anemia occurred in 32%, 11%, and 11% of patients, respectively. Only 2 of 15 available tumors stained positive for secreted protein acid rich in cysteine, and neither of these patients benefited from the therapy. nab-Paclitaxel was well tolerated, and it demonstrated preliminary evidence of activity in a subset of patients who progressed on gemcitabine-based therapy.

Laryngeal Cancer: A 2‐Year Follow‐up Study

Objective: 1) To report the process of management and 2-year disease-free survival statistics for laryngeal cancer cases presenting to a United Kingdom tertiary cancer center. 2) To investigate which modality of treatment is the most appropriate for specific stages of laryngeal cancer. Method: A retrospective cohort study was carried out on laryngeal cancer patients presenting to a tertiary head and neck center from 2007 to 2009. Information on primary tumor staging and management was collected using the Somerset Cancer Registry. Patient notes, imaging, and histology reports were consulted to complete data retrieval. Results: Forty-seven cases presented during the study period (2 stage-0, 8 stage-I, 12 stage-II, 13 stage-III, 12 stage-IV). Nodal disease was present in 10.6%, and 2.1% had metastatic disease at presentation. Overall 2-year disease-free survival was 100% for stage-0, 87.5% stage-I, 69.2% stage-II, 36.4% stage-III, and 32.2% for stage-IV disease. Stage-I/II cases were treated by transoral laser (36.8%) or radiotherapy (63.2%), with 85.7% and 83.3% 2-year disease-free survival rates, respectively. Stage-III/IV cases were treated by surgery (38.1%) or radiotherapy/chemoradiotherapy (61.9%) with 2-year disease-free survival rates of 62.5% and 21.4%, respectively. Conclusion: Early-stage disease is equally well treated with transoral laser or radiotherapy alone in line with other studies. Larynx preservation with chemoradiotherapy demonstrates significantly poorer outcomes compared to surgery in this study. Accurate contemporary data recording is required to allow critical review of treatment modalities.

Role of F18-FDG PET/CT in the Staging and Restaging of Esophageal Cancer: A Comparison with CECT

Esophageal cancer is one of the most fatal cancers principally because of its late presentation. CECT plays an important role in the staging of esophageal cancer but has some limitations. PET/CT which provides physiological information along with anatomical information and is a whole body imaging technique may therefore be a better alternative and thereby can facilitate selection or exclusion of patients for resection. The aim was to evaluate the performance of F18 FDG PET/CT in the staging and restaging of esophageal carcinoma compared to CECT using histopathologic findings and clinical follow-up as gold standard. Twenty eight patients with proven esophageal carcinoma, both preoperative and postoperative, were studied with CECT and F18 FDG PET/CT scan within an interval of 2weeks. The PET/CT scan was acquired after injection of 370MBq (10mCi) F18-FDG and was evaluated for areas of increased focal uptake. CECT scan of chest and abdomen was done after injection of iodinated non-ionic contrast media. CECT findings suggested stage-IV disease in 16/28 (57.14%) patients and non stage-IV disease in 12/28 (42.86%) patients, whereas PET/CT suggested stage-IV disease in 23/28 (82.14%) patients and non stage-IV disease in 5/28 (17.86%) patients. Total nine patients were upstaged by PET/CT compared to CECT, out of which 7 (25%) were correctly upstaged and 2 (7.14%) were falsely upstaged. PET/CT improved our ability to detect distant metastases in 25% of patients that was missed by CECT. So, the use of F18 FDG PET/CT in esophageal cancer can alter management in significant number of patients.

Incidence of Septate Uterus in Reproductive-Aged Women with and without Endometriosis

Incidence of Septate Uterus in Reproductive-Aged Women with and without Endometriosis

Fetoscopic laser coagulation for severe twin‐to‐twin transfusion syndrome: factors influencing perinatal outcome, learning curve of the procedure and lessons for new centres

To evaluate the effects of operator experience on perinatal outcome in a single centre. Prospective consecutive cohort study. Regional tertiary referral Fetal Medicine Centre in the UK. Pregnant women with monochorionic twin pregnancies complicated by severe twin-to-twin transfusion syndrome (TTTS) (at ≤26 completed weeks of gestatiuon) treated by fetoscopic laser coagulation (FLC) between October 2004 and November 2009. Pregnancy characteristics and outcomes were collected. Logistic regression analysis was employed to determine the effect of a priori defined variables on outcome. Perinatal survival (survival to 28 days or beyond) for one or more twins. There were 164 consecutive sets of monochorionic twins. The median gestational age (GA) at FLC was 20.4 weeks (interquartile range 18-22.1 weeks), the median interval from FLC to delivery was 88.5 days (interquartile range 53-101 days) and the median GA at delivery was 33.2 weeks (interquartile range 29.7-34.9 weeks). The overall survival was 62%; perinatal survival of one or more twins was 85%. These outcomes improved after about 61 procedures were performed, and after about 3.4 years of experience. Univariate logistic regression analysis indicated that Quintero stage-IV disease decreased (OR 0.26; 95% CI 0.10-0.69) and prolongation of GA at delivery increased the survival of the twins (OR 1.34; 95% CI 1.12-1.60) (P < 0.01). Increasing experience of the procedure by operator led to a significant increase in perinatal survival (P < 0.01; OR 4.59; 95% CI 1.84-11.44). Multivariate logistic regression analysis indicated that only GA at delivery increased survival overall (OR 1.34; 95% CI 1.12-1.60; P = 0.01). These data indicate that both relatively large numbers treated and experience with FLC minimises any adverse outcome in monochorionic pregnancies with severe TTTS.

Basaloid squamous cell carcinoma: Report of five cases

To document the clinical and histopathological characteristics of basaloid squamous cell carcinoma (BSCC). To add five new cases to the literature and compare them with another published series. retrospective review of five cases with the diagnosis of BSCC of the larynx. all the patients were male. They were heavy smokers and drinkers. Most of the tumours were supraglottic. Three patients presented with stage-IV disease and the other two with stage-I disease. Surgery supplemented with radiation was used in three patients, partial surgery was used in another case and radiation and associated chemotherapy in the other one. Eight neck dissections were performed, six of them were functional and the other two radical dissections. Two cases were found to have metastatic lymph nodes. There were not any distant metastases but two patients had tumoral relapse. BSCC has well defined histological features. Central comedonecrosis within the cells nests, cell with nuclear palisading and high-grade dysplasia in overlaying mucosa are the main characteristics.

Impact of breast surgery on survival in patients with distant metastases at initial presentation: a systematic review of the literature

According to current treatment standards, patients with metastatic breast cancer at diagnosis receive palliative therapy. Local treatment of the breast is only recommended if the primary tumor is symptomatic. Recent studies suggest that surgical removal of the primary tumor has a favorable impact on the prognosis of patients with primary metastatic breast cancer. We performed a systematic review of the literature to weigh the evidence for and against breast surgery in this patient group. Ten retrospective studies were found in which the use of breast surgery in primary metastatic breast cancer and its impact on survival was examined. The hazard ratios of the studies were pooled to provide an estimate of the overall effect of surgery, and the results and conclusions of the studies were analyzed. A crude analysis, without adjustment for potential confounders, showed that surgical removal of the breast lesion in stage-IV disease was associated with a significantly higher overall survival rate in seven of the ten studies, and a trend toward a better survival in the three remaining studies. Surgery of the primary tumor appeared to be an independent factor for an improved survival in the multivariate analyses from the individual studies, with hazard ratios ranging from 0.47 to 0.71. The pooled hazard ratio for overall mortality was 0.65 (95% CI 0.59-0.72) in favor of the patients undergoing surgery. This systematic review of the literature suggests that surgery of the primary breast tumor in patients with stage-IV disease at initial presentation does have a positive impact on survival. In order to provide a definite answer on whether local tumor control in patients with primary metastatic disease improves survival, a randomized controlled trial comparing systemic therapy with and without breast surgery is needed.

The burden of colorectal cancer: prevention, treatment and quality of services

JEL Classification I11 I12 I18BackgroundColorectal cancer (CRC) is one of the most common formsof cancer and is a substantial health burden in mostdeveloped countries, with high incidence and mortality incombination with moderate survival. It is often diagnosedlate due to the absence of screening programmes, lack ofknowledge about symptoms and/or a reluctance to seekmedical help once the symptoms have appeared. Althoughimprovements in outcomes over time have been made,compared with other high incidence cancers, such as breastcancer, overall survival for CRC remains relatively poor.However, early detection is feasible and for patients withearly disease, surgery alone can be curative. Chemotherapyis essential to provide a chance of cure for patients withmore advanced disease and during the past 10 years, anumber of new agents have been introduced, with a sub-sequent increase in life expectancy for patients with Stage-IV disease from 5 to over 20 months. However, facilitiesfor treatment, use of and adherence to clinical managementguidelines and access to new, effective treatments report-edly vary widely across OECD countries. Cancer spendingon CRC is difficult to disaggregate, but evidence suggeststhat treatment costs are high, particularly for Stage III or IVwhich are advanced stages of the disease. Most countriesalso appear to have, for the most part, little concerted effortwith regards to screening activities. Similarly, both publicand political interest in CRC activities appears minimal tonon-existent in some countries compared to the public/media profile of breast cancer, for example.The rationale for this supplementAlthough CRC burden varies within countries, in Europe itis the second most diagnosed form of cancer, accountingfor 13% of total cancer incidence, and it is also second incancer mortality, accounting for 12% of total cancers in2006 [1]. Over the past decade, incidence in developedcountries has been increasing, and is most likely to con-tinue to do so with ageing populations, while mortality hasdecreased somewhat but not as much as in other similarhigh-incidence, high-mortality cancers.Incidence and mortality differ significantly betweenEuropean countries, even countries that are geographicallyclose to each other. Southern Europe has the lowest inci-dence and mortality (Greece, Turkey), while Eastern Eur-ope has the highest (Czech Republic, Hungary, Slovakia),probably due to differences in lifestyle, stage at diagnosisand treatment. Similarly, males have higher incidence andmortality than females, relating to differences in screeningparticipation, physician-seeking behaviour as well as life-style. These variations suggest that country policy andsocietal norms play a large role in CRC development andultimately cancer burden.Although survival from CRC has increased over the pastdecade, largely due to improved treatments and standards,it still remains poorer in Europe than in North America.Evidence indicates that less than 55% of Europeansachieve 5-year CRC survival in comparison to over 75%

A Cumulative Series from 14 Western Countries Suggests That Rituximab Significantly Changed the Dismal Natural History of Intravascular Large B-Cell Lymphoma (IVL) .

Background: IVL is a typically disseminated and aggressive malignancy that results in severe multi-organ failure and poor survival. There are two well-recognized clinical forms of IVL (“classical” and “hemophagocytosis-related”) that exhibit significant clinical, biological and prognostic differences, with substantial variability between Japanese and Western patients (pts). Treatment with anthracycline-based chemotherapy is associated with disappointing results in both groups of pts (3-yr OS ~35%), but encouraging results of the addition of rituximab in a retrospective Japanese series were recently reported. Conversely, nothing is known on the efficacy and tolerability of rituximab in IVL pts diagnosed in Western countries since available information is limited to a few single case reports and a small retrospective series.Methods: To investigate the role of rituximab as upfront treatment for IVL in Western countries, we contacted all the authors of previous pertinent reports, asking for updated follow-up of their published and unpublished cases of IVL, treated with or without rituximab at their Institutions, from August 2002 to June 2008. Three-fourth of investigators replied, providing complete information and updated follow-up of 41 pts. Seven pts were excluded due to death before treatment initiation (n=2) and rituximab administration only after relapse/progression (n=5). The remaining 34 pts treated with rituximab, either alone (n=3) or in combination with anthracycline-based chemotherapy (n=31), constituted the study population.Results: Median age of the 34 pts was 65 yrs (range 20–86; 18 males), with ECOG-PS 3–4 in 32% of pts, elevated LDH levels in 86%, B-symptoms in 70%, and stage-IV disease in 73%, with bone marrow (35%), skin (32%) and CNS (26%; n=9) being the most commonly involved organs. Rituximab (375 mg/m2) was administered concurrently with the 1st course of chemotherapy (within the same day) in all pts except 2 (administered from the 2nd course); this information was not available in 2 cases. None of the patients received rituximab maintenance. Chemotherapy regimens included CHOP21 (n=29), CEOP21 (n=1) and CHOP14 (n=1). Upfront treatment included high-dose methotrexate in 1 of the 9 pts with CNS involvement; 4 of the 25 pts without CNS involvement at diagnosis received CNS prophylaxis (HD-MTX in 1; intrathecal chemo in 3). Twenty-nine pts (85%) completed the planned program; 2 pts died of infectious complications, 1 pt experienced disease progression, 1 pt interrupted chemotherapy for toxicity and proceeded with rituximab alone, 1 pt is still receiving treatment. Rituximab was generally well tolerated, with mild side effects in 4 pts (12%); it was discontinued due to severe toxicity only in 2 (6%) pts (pulmonary failure and coma after the first course). After treatment (n=33), 29 (88%) pts achieved a complete remission, with an ORR of 91%. At a median follow-up of 2 years, 6 pts experienced relapse, with CNS involvement in 5; only 1 of these pts had CNS disease at diagnosis. Twenty-eight pts are alive, with a 3-yr OS of 81%; 2 pts died of toxicity, 1 died of unrelated causes and only 3 pts died of lymphoma, all of them after CNS relapse.Conclusions: This is the largest cumulative experience with upfront rituximab in IVL pts diagnosed in Western countries. The addition of rituximab was safe in 94% of cases and significantly improved the dismal prognosis of IVL. CNS was the principal failure site after R-CHOP therapy. To reduce rituximab side effects, perhaps by administration delay of 3–4 days at the 1st course in pts with high tumour burden, and to improve CNS disease control by using drugs with a better CNS bioavailability are two advisable strategies to further improve therapeutic efficacy in pts with IVL.