Immune receptor inhibition through enforced phosphatase recruitment.

Antibodies that antagonize extracellular receptor-ligand interactions are used as therapeutic agents for many diseases to inhibit signalling by cell-surface receptors1. However, this approach does not directly prevent intracellular signalling, such as through tonic or sustained signalling after ligand engagement. Here we present an alternative approach for attenuating cell-surface receptor signalling, termed receptor inhibition by phosphatase recruitment (RIPR). This approach compels cis-ligation of cell-surface receptors containing ITAM, ITIM or ITSM tyrosine phosphorylation motifs to the promiscuous cell-surface phosphatase CD452,3, which results in the direct intracellular dephosphorylation of tyrosine residues on the receptor target. As an example, we found that tonic signalling by the programmed cell death-1 receptor (PD-1) results in residual suppression of T cell activation, but is not inhibited by ligand-antagonist antibodies. We engineered a PD-1 molecule, which we denote RIPR-PD1, that induces cross-linking of PD-1 to CD45 and inhibits both tonic and ligand-activated signalling. RIPR-PD1 demonstrated enhanced inhibition of checkpoint blockade compared with ligand blocking by anti-PD1 antibodies, and increased therapeutic efficacy over anti-PD1 in mouse tumour models. We also show that the RIPR strategy extends to other immune-receptor targets that contain activating or inhibitory ITIM, ITSM or ITAM motifs; for example, inhibition of the macrophage SIRPα 'don't eat me' signal with a SIRPα-CD45 RIPR molecule potentiates antibody-dependent cellular phagocytosis beyond that of SIRPα blockade alone. RIPR represents a general strategy for direct attenuation of signalling by kinase-activated cell-surface receptors.

A dramatic response to checkpoint inhibitor in a woman with small cell carcinoma of the hypercalcemic type of the ovary.

OBJECTIVE: We present the rare case of a 21 year old woman with small cell carcinoma of the right ovary of the hypercalcemic type with dramatic response to checkpoint inhibitor. METHODS: Case report. RESULTS AND CONCLUSIONS: Our patient, a 22-year old woman with small cell carcinoma of the hypercalcemic type with hepatic metastases, is currently 43 months under treatment with pembrolizumab. Last MRI revealed no viable liver metastases nor other signs of recurrence. This is the longest survival of a patient with small cell carcinoma of the ovary under therapy with checkpoint inhibitors reported in the literature so far. With this report we emphasize the importance of immunohistological testing for PD-L 1. Treating clinicians should keep off-label use of immune checkpoint blockade in mind when treating this highly aggressive tumor if all other treatment options fail.

A comparison of the outcomes of pulmonary versus extrapulmonary extensive-stage small cell carcinoma.

BACKGROUND: Extrapulmonary small cell carcinomas (EPSCCs) are rare cancers, comprising 0.1-0.4% of all cancers. The scarcity of EPSCC studies has led current treatment strategies to be extrapolated from small cell lung cancer (SCLC), justified by analogous histological and clinical features. AIMS: We conducted a retrospective cohort study comparing the outcomes of extensive-stage (ES) SCLC and EPSCC. METHODS: Patients diagnosed with ES SCLC or EPSCC between 2010 and 2020 from four hospitals in Sydney were identified. Patients who received active treatment and best supportive care were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS) and overall response rates (ORRs). RESULTS: Three hundred and eighty-four patients were included (43 EPSCC vs. 340 SCLC). EPSCC were of genitourinary (n = 15), unknown primary (n = 13) and gastrointestinal (n = 12) origin. Treatment modalities for EPSCC compared to SCLC included palliative chemotherapy (56% vs 73%), palliative radiotherapy (47% vs 59%) and consolidation chest radiotherapy (10% of SCLC). Overall, median OS was 6.4 versus 7 months for EPSCC versus SCLC respectively, but highest in prostate EPSCC (25.6 months). Of those who received chemotherapy (22 EPSCC vs 233 SCLC), median OS was 10.4 versus 8.4 months (HR OS 0.81, 95% confidence interval (CI): 0.5-1.31, P = 0.38); PFS was 5.4 versus 5.5 months (HR PFS 0.93, 95% CI: 0.58-1.46, P = 0.74) and ORR were 73% versus 68%. CONCLUSIONS: EPSCC and SCLC appeared to have comparable OS and treatment outcomes. However, the wide range of OS in EPSCC highlights the need for an improved understanding of its genomics to explore alternative therapeutics.

The impact of neo/adjuvant treatment choices on prognosis for surgically treated small-cell neuroendocrine carcinoma of the cervix.

Small-cell neuroendocrine carcinoma of the cervix (SCNCC) is a rare and aggressive tumor with a poor prognosis. Surgical resection followed by adjuvant therapy is the standard treatment for early-stage disease but the influence of different neo/adjuvant treatment approaches remains unclear. Retrospectively, we collected patients' characteristics and treatments in two medical centers. Disease status and survival outcomes were renewed through follow-up. Statistics analysis mainly included Kaplan-Meier methods for survival curve estimation, log-rank test for survival curve comparison, and Cox proportional hazards models for independent prognostic factors prediction. Finally, 51 patients treated by radical surgery between January 2010 and April 2020 were enrolled with a median age of 50 years (range: 32-68). 12 (23.5%) patients were at stage IIIC1 according to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging systems and the rest were at the early stage. The mean tumor size was 3.6±1.3 cm. Pathological examination found 24 cases with pure SCNCC and 27 cases with admixed SCCC. 29 (56.9%) patients had deep stromal infiltration and 19 (37.3%) patients had lymphovascular space invasion. 34 (66.7%) patients received neo/adjuvant chemotherapy and pelvic radiation was conducted in 41 (80.39%) patients with a median dose of 46 Gy (range: 40-50.4 Gy). The median follow-up time was 25.0 months. The median disease-free survival (DFS) time was 23.0 months. 27 (52.9%) patients developed distant metastasis and 14 (27.5%) experienced local failure. The median overall survival (OS) was 32.0 months. Univariate and multivariate analysis showed neoadjuvant chemotherapy as negative (HR=2.081, 95% CI 1.030-4.203, p=0.041) and adjuvant chemotherapy (HR=0.409, 95% CI 0.213-0.784, p=0.020) as positive independent prognostic factor for DFS. For OS, only lymph node metastasis was confirmed as an independent prognostic factor in both univariate analysis (HR=1.528, 95% CI 1.011-2.308, p=0.044) and multivariate analysis (HR=1.697, 95% CI 1.041-2.768, p=0.034). In conclusion, for surgically treated SCNCC, adjuvant chemotherapy showed a positive influence on DFS while neoadjuvant chemotherapy harmed DFS. OS was unaffected by either treatment choice.

[A Case of Successful Treatment of Small Cell Carcinoma of the Bladder with Pembrolizumab].

Small cell carcinoma of the bladder (SCCB) is a rare cancer that accounts for approximately 1% of primary malignant bladder tumors. It is highly malignant and has a poor prognosis. Similar to small cell lung cancer, platinum-based chemotherapy is recommended as the first-line therapy, and amrubicin (AMR) is recommended as the second-line therapy, but there is no established therapy after the second line. We report a case of SCCB that was refractory to multiple chemotherapies but responded to pembrolizumab. A 77-year-old male, diagnosed with clinical stage T3N0M0 small cell carcinoma and invasive urothelial carcinoma by transurethral resection of bladder tumor (TURBT), underwent robot-assisted radical cystectomy after three cycles of neoadjuvant cisplatin-irinotecan chemotherapy, and pathological examination revealed only small cell carcinoma in his cystectomy specimen. After three courses of adjuvant carboplatin-etoposide chemotherapy, the patient developed liver and bone metastases. Furthermore, after two courses of amrubicin, we started pembrolizumab due to the progression of metastases. Metastases decreased after starting pembrolizumab and continued to decrease after discontinuation because of immunerelated adverse events (irAEs). Therefore, pembrolizumab may be an option for the treatment of refractory SCCB.

Outcomes of extensive stage extrapulmonary small cell cancer.

BACKGROUND: Extrapulmonary small cell cancer (EPSCC) is a rare malignancy with an incidence of approximately 0.1%-0.4% of all cancers. Treatment of this disease is often based on small cell lung cancer. AIMS: We aimed to investigate real-world clinical outcomes of patients with extensive-stage (ES) ESPCC. METHODS: Patients diagnosed with ES EPSCC between 2010 and 2020 from multiple centres in New South Wales were identified. Patient, disease and treatment characteristics were collected and presented using descriptive statistics. Survival was analysed using the Kaplan-Meier method. Univariate and multivariate Cox regression hazard models were used to identify potential prognostic factors. RESULTS: Sixty eligible ES EPSCC patients were identified, including 65% male and 35% female. The mean age was 69 years (range 37-88). Forty-five per cent were never smokers, 42% ex-smokers and 13% current smokers, and 17% of patients had limited-stage disease prior to development of ES disease. The most common primary sites were genitourinary (42%; mainly prostate (n = 14) and bladder (n = 10)), gastrointestinal (28%; mainly oesophagus (n = 5) and colon (n = 4)) and unknown primary (22%). Treatments received included palliative chemotherapy (67%), palliative radiotherapy (53%), palliative surgery (13%) and best supportive care alone (13%). The median overall survival (OS) was 8.0 months. The median progression-free survival was 5.4 months, and response rate to first-line chemotherapy was 65%. Platinum-based chemotherapy was prognostic of longer OS (HR 0.27, CI 0.12-0.60, P = 0.001). CONCLUSIONS: Patients with ES EPSCC had good response to palliative chemotherapy, but OS remained poor. Further research is required to improve the prognosis in this population.

Cryptotanshinone inhibits oral squamous cell carcinoma through the autophagic pathway.

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors with a low quality of life. Because traditional surgical treatment often causes large wounds and then affects the quality of life of patients, it is urgent to find new and efficient drugs with good safety for clinical treatment. This study aimed to identify potential anticancer drugs starting from the traditional Chinese medicine Salvia miltiorrhiza extract. Cryptotanshinone, a compound isolated from the Chinese herb Salvia miltiorrhiza, was found to significantly induce apoptosis and inhibit proliferation in OSCC. By electron microscopy, autophagosomes were found. Confocal fluorescence microscopy data showed that cryptotanshinone significantly induced autophagy in OSCC cells. Mechanistically, the western blot assay indicated that cryptotanshinone induced cell autophagy through the activation of the LC3 pathway, whereas the autophagy inhibitor 3-methyladenine attenuated these effects. Furthermore, we demonstrated that cryptotanshinone had a significant antitumor effect in a tumor xenograft model, and no damage to vital organs was observed. Our findings provide evidence that cryptotanshinone may be a novel therapeutic strategy for the treatment of OSCC.

[A Case of Advanced Squamous Cell Carcinoma of the Lung 19 Years after Chemoradiotherapy of Limited-Disease Small-Cell Lung Cancer].

A 65-year-old man was referred to our hospital because of a fever and cough 19 years after chemoradiotherapy for small-cell lung cancer(SCLC)in the right middle lobe. Computed tomography(CT)revealed a normal right middle lobe, but found pneumonia and a tumor at the bronchial entrance of the right upper lobe. After treating the pneumonia with antibiotics and prednisolone, transbronchial biopsies(TBBs)revealed the tumor to be squamous cell carcinoma(SCC). Eight lines of chemotherapy including immune checkpoint inhibitors(ICIs)were completed with a 42-month survival following the initiation of chemotherapy for SCC, after which he ultimately died of hemoptysis. Survival of over 10 years from small- cell cancer is rare. We herein report the prognosis of SCLC and the treatment of subsequent primary lung cancer.

TP53 Null Mutations Identify Lung Cancer Cell Lines with Highest Sensitivity to the Nontaxane Microtubule Inhibitor Eribulin.

The nontaxane microtubule inhibitor eribulin is an approved therapeutic for metastatic breast cancer and liposarcoma. Eribulin was previously tested in unselected patients with lung cancer and yielded a modest objective response rate of ∼5%-12%. Because lung cancers represent diverse histologies and driving oncogenic mutations, we postulated that eribulin may exhibit properties of a precision oncology agent with a previously undefined specificity for a molecularly distinct subset of lung cancers. Herein, we screened a panel of 44 non-small cell and small-cell lung cancer cell lines for in vitro growth sensitivity to eribulin. The results revealed a greater than 15,000-fold range in eribulin sensitivity (IC50 = 0.005-89 nM) among the cell lines that was not correlated with their sensitivity to the taxane-based inhibitor paclitaxel. The quartile of cell lines exhibiting the lowest eribulin IC50 values was not enriched for specific histologies, epithelial-mesenchymal differentiation, or specific oncogene drivers but was significantly enriched for nonsense/frameshift TP53 mutations and low-TP53 mRNA but not missense TP53 mutations. By comparison, the mutation status of cyclin-dependent kinase inhibitor 2A, STK11, and KEAP1 was not associated with eribulin sensitivity. Finally, the highest eribulin IC50 quartile (>1 nM) exhibited significantly elevated mRNA expression of the drug pump, ATP binding cassette B1, defined resistance mechanism to eribulin, and paclitaxel. The findings support further investigations into basic mechanisms by which complete lack of TP53 function regulates anticancer activity of eribulin and the potential utility of TP53 null phenotypes distinct from TP53 missense mutations as a biomarker of response in patients with lung cancer. SIGNIFICANCE STATEMENT: Distinct from precision oncology agents that are matched to cancers bearing oncogenically activated versions of their targets, microtubule inhibitors, such as eribulin, are deployed in an unselected manner. The results in this study demonstrate that lung cancer cell lines exhibiting the highest sensitivity to eribulin bear TP53 null phenotypes, supporting a rationale to consider the status of this tumor suppressor in the clinical setting.

Chemotherapy with atezolizumab for small cell or neuroendocrine carcinoma of the prostate: A single institution experience.

INTRODUCTION: Chemotherapy in combination with immunotherapy has a proven survival benefit compared to chemotherapy alone in extensive stage small cell lung cancer (SCLC) and is the new standard of care. Since extrapulmonary small cell carcinomas (SCCs) are less common, treatment paradigms are reasonably extrapolated from SCLC regimens. We examined our institution's experience utilizing the combination of chemotherapy and immunotherapy (as used in SCLC) for SCC and neuroendocrine carcinoma of the prostate. METHODS: Utilizing an institutional database search tool, we queried the electronic medical record to identify patients with SCC or neuroendocrine carcinoma of the prostate who had been treated with atezolizumab and chemotherapy. We recorded patient characteristics, including age, pathology, and disease extent. Treatment characteristics included number of prior treatments, use of concominant androgen deprivation, number of cycles of immunotherapy, and prior systemic therapies (including those for adenocarcinoma of the prostate). Progression free survival (PFS) and overall survival (OS) were the primary outcomes. RESULTS: We identified seven men who received atezolizumab for metastatic prostate cancer with a small cell or neuroendocrine component. In six of the seven patients, the combination of carboplatin, etoposide, and atezolizumab was the first-line of treatment after diagnosis of small cell or neuroendocrine carcinoma. Two of the seven patients had de novo small cell/neuroendocrine pathology, while the other five had transformation from a preexisting adenocarcinoma. In the patients who received chemotherapy plus immunotherapy in the first-line setting, at a median follow-up of 6.5 months (range: 1.5-15.1) the median PFS was 3.4 months and median OS was 8.4 months. CONCLUSION: Small cell or neuroendocrine carcinoma of the prostate was associated with poor survival outcomes despite adding immunotherapy (atezolizumab) to chemotherapy (carboplatin and etoposide). To our knowledge, there has been no demonstrable benefit of adding immunotherapy to chemotherapy in this setting.

Re-assigning the histologic identities of COV434 and TOV-112D ovarian cancer cell lines.

OBJECTIVE: The development of effective cancer treatments depends on the availability of cell lines that faithfully recapitulate the cancer in question. This study definitively re-assigns the histologic identities of two ovarian cancer cell lines, COV434 (originally described as a granulosa cell tumour) and TOV-112D (originally described as grade 3 endometrioid carcinoma), both of which were recently suggested to represent small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), based on their shared gene expression profiles and sensitivity to EZH2 inhibitors. METHODS: For COV434 and TOV-112D, we re-reviewed the original pathology slides and obtained clinical follow-up on the patients, when available, and performed immunohistochemistry for SMARCA4, SMARCA2 and additional diagnostic markers on the original formalin-fixed, paraffin-embedded (FFPE) clinical material, when available. For COV434, we further performed whole exome sequencing and validated SMARCA4 mutations by Sanger sequencing. We studied the growth of the cell lines at baseline and upon re-expression of SMARCA4 in vitro for both cell lines and evaluated the serum calcium levels in vivo upon injection into immunodeficient mice for COV434 cells. RESULTS: The available morphological, immunohistochemical, genetic, and clinical features indicate COV434 is derived from SCCOHT, and TOV-112D is a dedifferentiated carcinoma. Transplantation of COV434 into mice leads to increased serum calcium level. Re-expression of SMARCA4 in either COV434 and TOV-112D cells suppressed their growth dramatically. CONCLUSIONS: COV434 represents a bona fide SCCOHT cell line. TOV-112D is a dedifferentiated ovarian carcinoma cell line.

Phase II study of pembrolizumab efficacy and safety in women with recurrent small cell neuroendocrine carcinoma of the lower genital tract.

OBJECTIVE: To investigate the efficacy and safety of pembrolizumab in women with recurrent small cell neuroendocrine tumors of the lower genital tract. METHODS: We conducted an open-label, investigator-initiated phase II basket trial of pembrolizumab 200 mg intravenously every 3 weeks in patients with rare tumors (ClinicalTrials.gov: NCT02721732). The trial had prespecified cohorts, including small cell malignancies of extrapulmonary origin. Eligibility criteria included disease progression during standard treatment in the 6 months before study enrollment. Patients were enrolled from February 2017 to February 2019. The primary endpoint was the proportion of patients alive without progression at 27 weeks. Response to pembrolizumab was evaluated every 9 weeks (3 cycles) with radiographic imaging. RESULTS: Seven women with gynecologic extrapulmonary small cell carcinoma were enrolled, 6 with cervical and 1 with vulvar carcinoma. No patient was progression free at 27 weeks. At first radiologic assessment, 1 patient had stable disease, while 6 had progression. The single patient with stable disease at 6 weeks had disease progression at 14 weeks. The median progression-free interval was 2.1 months (range 0.8-3.3 months). Severe treatment-related adverse events (≥grade 3) were seen in 2 of 7 patients (29%); 1 patient had grade 3 asymptomatic elevation of serum alkaline phosphatase, and 1 had grade 3 asymptomatic elevation of serum alanine aminotransferase. CONCLUSIONS: Pembrolizumab alone showed minimal activity in women with recurrent small cell neuroendocrine tumors of the lower genital tract. Treatment was well tolerated in the majority of study participants, and the rate of severe adverse events was low.

Small cell carcinoma of the uterine cervix: a multi-institutional experience.

OBJECTIVE: Small cell carcinoma of the uterine cervix is associated with a poor prognosis with a median overall survival that is quite low. The aim of this study was to determine the clinico-pathologic characteristics that have an impact on survival in patients with small cell carcinoma of the uterine cervix. METHODS: A total of 93 patients were involved in this retrospective study. Inclusion criteria were patients diagnosed with histopathologically confirmed small cell carcinoma of the uterine cervix and then later treated at three participating centers, between June 2001 and March 2015. Those without complete available follow-up records were excluded. The endpoints of this study were disease-free survival and overall survival. Kaplan-Meier and Cox regression methods were used for analyses. RESULTS: There were statistical differences in overall survival between patients in early and in advanced stages by using the 2009 International Federation of Gynecology and Obstetrics (FIGO) clinical stage. There were 75 patients with FIGO stage I to IIA (56 patients stage I, 17 patients stage IIA, and two patients stage IB or IIA because of uncertainty as to whether the fornix was involved); and 18 patients with FIGO stage IIB and above (10 patients IIB stage, five patients stage III, and three patients stage IV). Among the 76 patients who had surgery, 73 (96%) had a radical hysterectomy with pelvic lymph node dissection and three (4%) patients had a simple hysterectomy without lymph node dissection. For early-stage patients, the 5 year disease-free survival rate was 52.7% compared with 32.4% in the advanced stage group (p=0.022). The disease-free survival for the early-stage group was 64.4% compared with 36.7% in the advanced-stage group (p=0.047). For factors affecting overall survival, age at diagnosis, tumor homology, tumor size, depth of stromal invasion, lymph node involvement, and treatment modality failed to reach significance in both univariate and multivariate analysis. CONCLUSION: FIGO stage was a prognostic factor impacting survival-both overall survival and disease-free survival. Age at diagnosis, tumor histology (pure or mixed), tumor size, depth of stromal invasion, lymph node involvement, and treatment modality did not have an impact on overall survival.

[A Case of Small Cell Carcinoma of the Bladder].

A 74-year-old man presented with further treatment for muscle invasive small cell carcinoma of the bladder. After three courses of neoadjuvant chemotherapy with cisplatine + etoposide (EP), total cystectomy was performed. The pathological findings revealed small cell carcinoma of the bladder (ypT2N0M0). Eleven months after the operation, thoracoabdominal computed tomography (CT) showed right pelvic lymph node metastasis. He underwent 9 courses of EP chemotherapy, and everolimus, finally, Amrubicin was administered. Amrubicin might be useful for small cell carcinoma of the bladder.

A retrospective study of definitive chemoradiotherapy in patients with resectable small cell neuroendocrine carcinoma of the esophagus.

BACKGROUND: Standard treatment for resectable small cell neuroendocrine carcinoma of the esophagus (SCNEC-E) remains to be established. METHODS: We retrospectively studied 7 consecutive patients with resectable SCNEC-E who received definitive chemoradiotherapy (dCRT) to evaluate the safety and efficacy. Treatment consisted of two courses of chemotherapy with cisplatin (80 mg/m2 on day 1) and etoposide (100 mg/m2 on days 1-3) or carboplatin (AUC 5 on day 1) and etoposide (80 mg/m2 on days 1-3) given every 4 weeks during dCRT. The total radiation dose was 50.4 Gy (28 fractions). RESULTS: The clinical stage was IA in 1 patient, IB in 2 patients, IIA in 3 patients, and IIB in 1 patient. Definitive CRT was completed in all patients. The median overall treatment time of radiotherapy was 44 days. The chemotherapy regimen included in dCRT was cisplatin and etoposide in 3 patients and carboplatin and etoposide in 4 patients. Acute adverse events of grade 3 or 4 were neutropenia 100%, thrombocytopenia 43%, febrile neutropenia 43%, and nausea 14%. There were no late grade 3 or 4 adverse events. The median survival time was 32 months. The complete response rate was 100%. The recurrence rate was 43%. The median survival of the 4 patients without recurrence was 56 months. CONCLUSIONS: Definitive CRT with cisplatin and etoposide or carboplatin and etoposide is a feasible treatment for the resectable SCNEC-E, and long-term survival can be achieved in some patients.

Biallelic tumour suppressor loss and DNA repair defects in de novo small-cell prostate carcinoma.

Small-cell prostate carcinoma (SCPC) is an aggressive malignancy that is managed similarly to small-cell lung cancer. SCPC can evolve from prostate adenocarcinoma in response to androgen deprivation therapy, but, in rare cases, is present at initial cancer diagnosis. The molecular aetiology of de novo SCPC is incompletely understood, owing to the scarcity of tumour tissue and the short life-expectancy of patients. Through a retrospective search of our regional oncology pharmacy database, we identified 18 patients diagnosed with de novo SCPC between 2004 and 2017. Ten patients had pure SCPC pathology, and the remainder had some admixed adenocarcinoma foci, but all were treated with first-line platinum-based chemotherapy. The median overall survival was 28 months. We performed targeted DNA sequencing, whole exome sequencing and mRNA profiling on formalin-fixed paraffin-embedded archival tumour tissue. We observed frequent biallelic deletion and/or mutation of the tumour suppressor genes TP53, RB1, and PTEN, similarly to what was found in treatment-related SCPC. Indeed, at the RNA level, pure de novo SCPC closely resembled treatment-related SCPC. However, five patients had biallelic loss of DNA repair genes, including BRCA1, BRCA2, ATM, and MSH2/6, potentially underlying the high genomic instability of this rare disease variant. Two patients with pure de novo SCPC harboured ETS gene rearrangements involving androgen-driven promoters, consistent with the evolution of de novo SCPC from an androgen-driven ancestor. Overall, our results reveal a highly aggressive molecular landscape that underlies this unusual pathological variant, and suggest opportunities for targeted therapy strategies in a disease with few treatment options. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

[Prognostic evaluation of nutritional indicators in patients with limited-stage small cell lung cancer].

Objective: To explore the effect of nutritional status pre-and during chemoradiotherapy on the prognosis of patients with limited- stage small cell lung cancer (LS-SCLC). Methods: We retrospectively collected medical records of 172 LS-SCLC patients undergoing concurrent chemoradiotherapy in our hospital from 2000 to 2014, with 126 males and 46 females. The data of complete blood count and hepatic and renal function were collected before initial treatment, before radiotherapy, 4 weeks during radiotherapy, and 1 month after complete of treatment. The prognostic nutritional index(PNI)was calculated. Kaplan-Meier method was used to calculate the survival rate. Log-rank test was performed used to compare the survival differences between groups. Multivariate prognostic analysis was performed using Cox regression model. Results: The median overall survival (OS) was 21 months, with median progression-free survival (PFS) of 11 months. At the beginning of treatment, patients with pre-treatment PNI ≥ 53 had significantly superior OS (median 37 vs 15 months, P=0.001) and PFS (median 16 vs 10 months, P=0.017). Patients with pre-treatment hemoglobin ≥140 g/L and <140 g/L had an median OS of 32 months and 17 months (P=0.019), and median PFS of 16 months and 9 months (P=0.040), respectively. During chemoradiation, patients with elevated hemoglobin had similar median OS compared with those had decreased hemoglobin (27 vs 18 months, P=0.063, but superior median PFS (15 vs 9 months, P=0.017). Multivariate analysis revealed that prophylactic cranial irradiation, pre-treatment hemoglobin ≥140 g/L, and pretreatment PNI ≥53 were independent predictors of OS and PFS in patients with LS-SCLC. Conclusion: Pre-treatment nutritional status and the changes of nutritional status during chemoradiotherapy is significantly associated with the prognosis of patients with limited-stage small cell lung cancer. The patients with better pre-treatment nutritional status have a better prognosis.

[A Case of Small Cell Carcinoma of the Pancreas].

A 55-year-old man was admitted to our hospital for jaundice. Magnetic resonance cholangiopancreatography showed a mass in the pancreatic head as well as biliary obstruction. We strongly suspected invasive ductal carcinoma of the pancreas. We performed pancreaticoduodenectomy with partial resection of the portal vein. The histopathological diagnosis was small cell carcinoma of the pancreas. We detected metastasis of the right hilar lymph node in PET-CT scan performed 2 months after the surgery and started chemotherapy with cisplatin(CDDP)plus irinotecan(CPT-11). However, we observed recurrent metastasis of the right hilar lymph node 12 months after the surgery. We started second-line chemotherapy with amrubicin( AMR)and radiotherapy. Unfortunately, the patient died from multiple metastases of the left adrenal gland and brain 26 months after the surgery. The prognosis of small cell carcinoma of the pancreas is extremely poor. Multimodal treatment such as chemotherapy, radiotherapy, and curative operation are required for long-term survival.

[A Case of Gastric Small Cell Carcinoma with Rapid Regrowth after Surgery].

The patient was a 59-year-old man with type 2 advanced gastric cancer in the antrum. Abdominal computed tomography revealed the primary tumor with regional lymph node metastasis. Distal gastrectomy and D2 lymph node dissection were performed. Histopathological findings indicated gastric small cell carcinoma. Lymph node metastasis was observed microscopically in the #6 lymph nodes. Peritoneal lavage cytology was positive. The pathologic stage of the disease was pT2(MP), med, INF b, ly2, v2, pPM0, pDM0, pN2(6/33: #5, #6), M1, P0, CY1, H0, stage Ⅳ, R1(cy+). After surgery, he received chemotherapy with capecitabine plus oxaliplatin. However, after 1 course of therapy the disease had progressed, and the patient was diagnosed with peritoneal metastasis. Chemotherapy of CDDP plus CPT-11 was initiated, and after 5 courses the patient died.