Cisplatin-etoposide Chemotherapy Research Articles

An aggressive Cushing's syndrome originating from a rare thymic neuroendocrine tumor, controlled successfully with fluconazole and octreotide therapy before surgery.

Cushing's syndromes (CSs) due to the thymic neuroendocrine tumors are rarely seen. Here, a case of ectopic CS originating from an atypical neuroendocrine tumor has been presented. A 49-year-old woman was hospitalized with symptoms of fatigue, chest pressure, dyspnea, muscle weakness, and resistant hypertension. There was marked hyperpigmentation in the whole-body surface suggestive of adrenocorticotropic hormone (ACTH) excess and there were physical features of CS. There was deep hypokalemia. Basal hormone profile, dexamethasone suppression tests, midnight cortisol, and 24-hour urine cortisol levels were suggestive of ectopic CS. The pituitary magnetic resonance imaging revealed a 5 mm cystic lesion and the patient refused inferior petrosal sinus sampling. Thorax computerized tomography showed an anterior mediastinal mass. A fluorodeoxyglucose-positron emission tomography showed the same mediastinal lesion (suvmax: 11.4), and no other tumor focus was detected. There was an aggressive cortisol excess causing acute respiratory distress syndrome, making it difficult to perform the surgery. We immediately started fluconazole and octreotide therapy and were successful in lowering the cortisol level. Then a complete resection of the tumor had been able to be surgically performed and tumor cells showed strong cytoplasmic immunopositivity with ACTH. A definitive diagnosis of "ACTH secreting atypical thymic carcinoid tumor" was rendered based on the histopathological and immunohistochemical features. There was only surrounding vessel invasion, and no lymphoid or other organ metastases were detected. As there were surrounding vessel invasions, a two-cycle regimen cisplatin-etoposide chemotherapy and radiotherapy were employed. After surgical and medical therapy, the cortisol and ACTH levels turned to normal. The patient is in biochemical and clinical remission and has no tumor recurrence yet. Ectopic ACTH-producing thymic carcinoids are rare but life-threatening tumors because of the underlying malignancy and severe hypercortisolemia. It is important to consider this disease and perform appropriate treatment at the right time. Today, surgery is the standard therapeutic modality if it is possible to perform, but there is not a clear and constant recommendation for nonsurgical therapeutic modalities. Further studies are needed for the optimal treatment strategies.

Selective fluorescence turn-on detection of combination cisplatin-etoposide chemotherapy based on N-CDs/GSH-CuNCs nanoprobe.

Cisplatin (CIS) and etoposide (ETP) combination therapy is highly effective for treating various cancers. However, the potential for pharmacokinetic interactions between these drugs necessitates selective sensing methods to quantitate both CIS and ETP levels in patient's plasma. This work develops a dual fluorescence probe strategy using glutathione-capped copper nanoclusters (GSH-CuNCs) and nitrogen-doped carbon dots (N-CDs) for the simultaneous analysis of CIS and ETP. The fluorescence signal of GSH-CuNCs at 615 nm increased linearly with CIS concentration while the N-CD emission at 480 nm remained unaffected. Conversely, the N-CD fluorescence was selectively enhanced by ETP with no interference with the CuNC fluorescence. Extensive materials characterization including UV-vis, fluorescence spectroscopy, XRD, and TEM confirmed the synthesis of the nanoprobes. The sensor showed high sensitivity with limits of detection of 6.95 ng mL-1 for CIS and 7.63 ng mL-1 for ETP along with excellent selectivity against potential interferences in rabbit plasma. Method feasibility was demonstrated with application to real rabbit plasma samples. The method was further applied to estimate the pharmacokinetic parameters of CIS before and after ETP coadministration. The dual nanoprobe sensing strategy enables rapid and selective quantitation of CIS and ETP levels to facilitate therapeutic drug monitoring and optimization of combination chemotherapy regimens.

Comparison of Simultaneous Integrated Boost IMRT for Dose Escalation (54 Gy) and Conventional IMRT (45 Gy) Twice Daily Combined with Concurrent Chemotherapy for Limited-Stage Small-Cell Lung Cancer: Analysis of Two Prospective Trials

<h3>Purpose/Objective(s)</h3> Twice-daily thoracic radiotherapy (TRT) with concurrent chemotherapy is standard for limited-stage small-cell lung cancer (LS-SCLC). However, the importance of twice-daily simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) has not been clearly defined in LS-SCLC. Therefore, we conducted a prospective single arm, multicenter phase II study of SIB-IMRT for dose escalation (54 Gy) to the gross tumor volume for LS-SCLC. Here, we compared SIB-IMRT for dose escalation (54 Gy) to the gross tumor volume versus conventional intensity-modulated radiotherapy (IMRT) of standard-dose (45 Gy) twice-daily combined with concurrent chemotherapy in patients with LS-SCLC. <h3>Materials/Methods</h3> Sixty patients with LS-SCLC were entered from 2015 to 2021 in the phase II study of SIB-IMRT, and all 60 patients were treated with SIB-IMRT to the postchemotherapy tumor volume, as the SIB-IMRT group. In the SIB-IMRT group, the prescribed dose was 54Gy at 1.8 Gy twice daily to PGTV, and 45 Gy at 1.5 Gy twice daily to PCTV. We previously conducted a prospective phase III study on thoracic radiotherapy (TRT) target volumes for LS-SCLC (Cancer, 2020, 126(4), 840-849). In that study, from 2012-2017, 85 patients received thoracic IMRT to the postchemotherapy tumor volume, as the IMRT group. In the IMRT group, the prescribed dose was 45 Gy at 1.5 Gy per twice-daily fraction to both the planning gross tumor volume (PGTV) and the planning clinical tumor volume (PCTV). All of the 145 patients in both groups received concurrent chemoradiotherapy (CCRT) after completion of 2 cycles of induction cisplatin-etoposide chemotherapy, and received chemotherapy for 4 to 6 cycles in total. We compared progression free survival (PFS) and overall survival (OS) between the treatment groups by using the Kaplan-Meier method. <h3>Results</h3> Overall, with a median follow-up of 34.6 months, the median PFS and OS were 11.9 and 23.7 months, respectively. The patients in the SIB-IMRT group showed marginal longer PFS than those in the IMRT group (13.3 months versus 11.5 months; <i>p</i> = 0.08). The median OS of the SIB-IMRT and IMRT groups were 35.0 and 20.3 months, with the 2-year OS rate of 66.1% and 38.8%, respectively (<i>p</i> =0.007). For radiotherapy toxicity, grade 2 acute esophagitis was more common in the SIB-IMRT group, but grade≥3 esophagitis and grade≥2 pneumonitis was no difference in both two groups. <h3>Conclusion</h3> For LS-SCLC patients, SIB-IMRT for dose escalation (54 Gy at 1.8Gy twice daily) to PGTV benefited survival greatly. Our results suggest that SIR-IMRT is safe and effective for patients with LS-SCLC and should be further evaluated in a large prospective clinical trial.

Evaluating Radiation-Related Risk Factors for Pneumonitis in Patients with Stage III NSCLC Receiving Durvalumab after Definitive Chemoradiation

<h3>Purpose/Objective(s)</h3> Concurrent chemoradiotherapy (CCRT) followed by durvalumab consolidation up to 12 mo became the standard of care for patients (pts) with stage III NSCLC after the publication of the PACIFIC trial. Both radiation pneumonitis (RP) and immune checkpoint inhibitor pneumonitis (ICI-p) are serious toxicities that can occur in this population, and radiation and ICI modality individually is known to contribute to pneumonitis risk; when combined, they could work synergistically or additively to increase this risk. We set out to evaluate radiation treatment specific risk factors for symptomatic pneumonitis in pts receiving CCRT followed by durvalumab. We hypothesize that adjuvant ICI (durvalumab) will increase the pneumonitis risk from CCRT predicted by current consensus guidelines. <h3>Materials/Methods</h3> We conducted a retrospective study of pts with stage III NSCLC treated with CCRT followed by durvalumab from 2018 -21. Median follow up time was 18.8 mo from the last day of RT to last contact. RT dose parameters were extracted from each treatment plan. Normal lung volume (NLV) was defined as total lung volume minus clinical target volume (Lung -CTV). Percentage of NLV receiving more than 5, 10, or 20 Gy (V5, V10, V20), and mean lung dose (MLD) were calculated. The primary endpoint was development of symptomatic pneumonitis (≥gr 2), assessed via clinical presentation and available imaging. The association between the % NLV of radiation and the probability of developing pneumonitis was analyzed using logistic regression, and odds ratios (OR) were estimated. <h3>Results</h3> Of the 80 patients included in this study, 21 (26.3%) developed symptomatic pneumonitis following durvalumab initiation. 69 (86.3%) received carboplatin-paclitaxel and 11 (13.8%) received cisplatin-etoposide chemotherapy. 73 (91.2%) had received standard RT dose of 60 Gy, while 7 (8.8%) received an additional 12-16 Gy SBRT boost to the primary tumor on a separate study. We found no significant association between symptomatic pneumonitis and RT dose or type of chemotherapy. However, smaller treatment volumes receiving 5 or 10 Gy were associated with lower pneumonitis risk: V10 < 40%, vs ≥ 40% (OR = 0.347, 95% CI 0.11-1.07, P=0.067) and V5 <65% vs ≥65% (OR = 0.42, 95% CI: 0.15-1.17, P = 0.096). Mean MLD was 14.9 Gy (3.9-21.9 Gy), Mean V20 was 25.7% (4.5-40.1%), both well below current consensus guidelines. We did not identify a notable association between pneumonitis and other known clinical risk factors. <h3>Conclusion</h3> This data is from our institution's first cohort of pts treated as in the PACIFIC study after durvalumab was approved by FDA for this indication. Our data suggest pts with a lower radiation treatment volume at 5 or 10 Gy (V5/V10) prior to durvalumab may have a lower risk of developing pneumonitis when other parameters (MLD, V20) are kept under the current recommended radiation tolerance without adjuvant ICI. Further research with larger study populations is needed to confirm this and inform guideline development.

A Real-World Evaluation of Atezolizumab Plus Platinum-Etoposide Chemotherapy in Patients With Extensive-Stage SCLC in Canada

IntroductionThe real-world data evaluating treatment outcomes of atezolizumab plus carboplatin-etoposide chemotherapy (atezolizumab) for extensive-stage SCLC (ESCLC) are lacking. Our objective was to evaluate real-world outcomes of ESCLC treated with atezolizumab. MethodsA retrospective analysis of provincial patients with ESCLC who started first-line (1L) systemic treatment was conducted. We primarily evaluated the progression-free survival (PFS) and overall survival (OS) outcomes in association with atezolizumab compared with platinum-etoposide chemotherapy (chemotherapy) while adjusting for relevant demographic and clinical factors. Adverse events (AEs) during 1L were evaluated. ResultsA total of 67 patients were identified. Of the 34 patients who received atezolizumab, 24% had Eastern Cooperative Oncology Group performance status greater than or equal to 2, approximately 50% were more than or equal to 65 years, 21% received cisplatin-etoposide chemotherapy before atezolizumab, and 12% had thoracic radiation (tRT).Within the atezolizumab versus chemotherapy group, the median PFS equals to 6.0 versus 4.3 months (p = 0.03) whereas OS = 12.8 versus 7.1 months (p = 0.01). Relative to chemotherapy, the hazard ratio (95% confidence interval) for PFS was 0.53 (0.28–1.02) and OS was 0.42 (0.20–0.88) with atezolizumab. tRT compared with no tRT receipt correlated with reduced death risk (hazard ratio [95% confidence interval] = 0.33 [0.13–0.88]).AE-related treatment withdrawal with atezolizumab was 32% and 15% with chemotherapy (p = 0.02). Within the tRT subgroup, 25% versus 20% in atezolizumab versus chemotherapy group, respectively, discontinued 1L owing to AE. ConclusionsThis is the first real-world study revealing comparable survival with that in the IMpower133 trial. Treatment discontinuation from AEs was higher with atezolizumab among Canadian patients with ESCLC. Our data suggest safe use of tRT and chemoimmunotherapy, but its efficacy for ESCLC warrants further study.

Survival and prognostic factors in adult medulloblastoma: the Salah Azaiz Institute experience

Background Medulloblastoma is the most common malignant brain tumor in children. This entity in adulthood is rare. The aim of our study is to evaluate therapeutic results and prognostic factors of adult medulloblastoma treated at our institute with post-operative radiotherapy. Methods We retrospectively reviewed a cohort of 55 patients with medulloblastoma who underwent radiation in the department of radiation oncology of institute Salah Azaiz (Tunis) over a 18-year period (1994–2012). Results The surgery was total or subtotal resection in 73% of cases. Forty-eight patients received radiotherapy to the entire craniospinal axis as part of the curative treatment. The median interval from surgery to the initiation of radiotherapy was 83 days. Etoposide-cisplatin chemotherapy was only performed in metastatic patients (n = 4). The 5-years and 10-years overall survival rates were respectively 53 and 34%. The dose of radiotherapy to the craniospinal axis was a prognostic factor. The 5-years and 10-years event-free-survival rates were 64 and 41%. Reduction in the dose of radiotherapy to the craniospinal axis and fourth ventricular floor involvement were correlated with a worse event-free survival. Conclusion Our results, compared to those of the literature, conclude that the reduction in the dose of radiotherapy to the craniospinal axis (<34 Gy) in the standard risk group of adult medulloblastoma could not be done without chemotherapy. In the high-risk group of adult medulloblastoma, radiotherapy to the cerebrospinal axis at the dose of 36 Gy with chemotherapy, is required for disease control.

MYCN drives chemoresistance in small cell lung cancer while USP7 inhibition can restore chemosensitivity.

Small cell lung cancer (SCLC) is an aggressive neuroendocrine cancer characterized by initial chemosensitivity followed by emergence of chemoresistant disease. To study roles for MYCN amplification in SCLC progression and chemoresistance, we developed a genetically engineered mouse model of MYCN-overexpressing SCLC. In treatment-naïve mice, MYCN overexpression promoted cell cycle progression, suppressed infiltration of cytotoxic T cells, and accelerated SCLC. MYCN overexpression also suppressed response to cisplatin-etoposide chemotherapy, with similar findings made upon MYCL overexpression. We extended these data to genetically perturb chemosensitive patient-derived xenograft (PDX) models of SCLC. In chemosensitive PDX models, overexpression of either MYCN or MYCL also conferred a switch to chemoresistance. To identify therapeutic strategies for MYCN-overexpressing SCLC, we performed a genome-scale CRISPR-Cas9 sgRNA screen. We identified the deubiquitinase USP7 as a MYCN-associated synthetic vulnerability. Pharmacological inhibition of USP7 resensitized chemoresistant MYCN-overexpressing PDX models to chemotherapy in vivo. Our findings show that MYCN overexpression drives SCLC chemoresistance and provide a therapeutic strategy to restore chemosensitivity.

Small cell carcinoma of gall bladder: An uncommon histologic entity

Gall bladder small cell carcinoma (scc) comprises of 0.5% of all GB cancers. It carries a poor prognosis in view of its aggressive nature. We here report a case of small cell carcinoma GB 55-year old lady presented with features of obstructive jaundice with significant weight loss. Examination revealed hard lump in right upper abdomen with multiple scratch marks all over the body. Clinically she had jaundice. Blood investigations revealed hyperbilirubinemia. Tumour markers showed raised CA 19-9. Staging CECT thorax and Abdomen reported polypoidal enhancing wall thickening of gall bladder with multiple metastatic deposits close to pancreatic head encasing main portal vein and common bile duct. Histopathology was suggestive of small cell carcinoma. Patient was referred to Oncology department and is receiving palliative cisplatin-etoposide chemotherapy

Management of “Ultra-High Risk” Gestational Trophoblastic Neoplasia at a Tertiary Center in India

Abstract Aims: The aim of this study is to identify clinicopathological features associated with increased morbidity and mortality in cases of “ultra-high risk” gestational trophoblastic neoplasia (GTN) and to compare initial low-dose etoposide-cisplatin (EP) induction chemotherapy with respect to etoposide methotrexate adriamycin cyclophosphamide vincristine (EMACO) regimen. Settings and Design: This was a retrospective study of patients of high-risk GTN from January 2012 to December 2016 with criteria mentioned as “ultra-high-risk group;” pathological or suspected diagnosis of choriocarcinoma, multiple (&gt;20) pulmonary metastases or associated with hemoptysis, brain metastases, large-volume liver metastases, profuse vaginal bleeding, human chorionic gonadotropin &gt;1000,000 IU/L, interval since the last antecedent pregnancy of &gt;2.8 years. Subjects and Methods: Comparison between the two groups of chemotherapy regimens and the median number of chemotherapy courses required to achieve complete remission was done Statistical Analysis Used: Data were analyzed using the SPSS software version 18 and Fisher's exact test with P value statistically significant at the level of 0.05. Results: Thirty-seven cases were high-risk GTN and 24 were “ultra-high risk.” The higher percentage of patients underwent remission of disease following low-dose induction chemotherapy as compared to primary EMACO therapy, 71.4% versus 58.8%. No resistance to second-line chemotherapy was noted, and no surgical intervention was required in the patients receiving low-dose induction chemotherapy before EMACO. Conclusions: We noted a decrease in the proportion of patients developing resistance to primary chemotherapy and lesser adverse effects in those receiving initial low-dose induction EP chemotherapy.

Pathological features, clinical presentations and prognostic factors of ovarian large cell neuroendocrine carcinoma: a case report and review of published literature

BackgroundThere is no consensus on the optimal chemotherapy regimen and the prognostic factors for ovarian large cell neuroendocrine carcinoma (LCNEC), a rare type of tumor. The objective of the present study is to present the case of a recent encounter of pure ovarian LCNEC and perform a brief review to summarize the clinicopathological features and prognostic factors of 57 cases of LCNEC patients that have been previously reported.Method: case presentationEligible studies were searched for online and 57 cases with clear follow-up data were found to have been reported. We present the 58th case, which is of a 70-year-old woman with stage IIIc primary pure LCNEC of the ovary. The initial symptom of this patient was abdominal distension (more than 2 months). A recent ultrasound test showed a solid-cystic mass occupying the pelvic and abdominal cavity. She received two courses of cisplatin-etoposide chemotherapy as an adjuvant therapy. No signs of nonclinical or radiological evidence of disease recurrence was found at follow-up examinations during the first 3 months after operation. A retrospective review of these 58 cases was conducted and survival curves were estimated. Using the Kaplan-Meier method.ConclusionThe patients included were aged between 18 and 80 years. A Kaplan-Meier survival curve revealed that the median overall survival was 10.000 months, while 26 (44.83%) patients died within 12 months. We compared the overall mean survival time of all patients with that of stage I patients (42.418 vs 42.047 months), which suggests that ovarian LCNEC has a very poor prognosis even at stage I. Mean survival was longer for patients who had undergone postoperative chemotherapy than for those without postoperative chemotherapy (48.082 vs 9.778 months). A small series, such as this, does not provide adequate data to establish a firm correlation between the postoperative chemotherapy and prognosis (p = 0.176). In our review of 58 cases with ovarian LCNEC, prognosis was unfavorable in most cases. Given the rarity of LCNEC, it is highly recommended that a global medical database of ovarian LCNEC and a standard system of diagnosis and treatment is established.

Immunotherapeutic approach to a case of advanced hepatoid adenocarcinoma of the lung

Hepatoid adenocarcinoma (HAC) is an extrahepatic primary tumor that expresses morphological features resembling hepatocellular carcinoma. This rare malignant tumor has been described in the gastrointestinal (GI) tract, the testes, the ovaries, and rarely, the lungs. Despite there being no standardized management protocol for this case with poor prognosis, the literature describes responses to treatment with cisplatin–etoposide chemotherapy. We present an updated review of all cases of HAC of the lung and the favorable results of a novel management method for this type of tumor. A table including all the HAC of the lung cases on the electronic database PubMed since 1980 is compiled. Here we present a case of primary HAC of the lungs, initially managed with cisplatin–etoposide without favorable response to treatment. The immunohistochemical profile of the tumor allowed for the novel use of immunotherapy in the setting of primary lung HAC, with favorable response. The case presented here is of interest as it adopts a novel immunotherapeutic approach to HAC, yielding a promising outcome. This highlights the importance of molecular typing and immunohistochemical profiling in the diagnosis and management of non-small cell lung cancer.

Outcome of patients with stage 2 or stage 3 seminoma treated with 3 cycles of cisplatin-etoposide chemotherapy (EP120): Updated data from a single center retrospective study.

e16061 Background: Metastatic seminoma is eminently treatable with platinum-based chemotherapy with either 3 cycles of BEP—bleomycin (B), etoposide (E) and cisplatin (P)—or 4 cycles of EP, achieving remission in more than 95% of the patients. However, bleomycin has a substantial toxicity profile and can cause life-threatening lung toxicity. Whether similar cure rates can be achieved without exposing patients to bleomycin is still undetermined. We describe our 19-year experience of treating patients with stage 2 or stage 3 seminoma with 3 cycles of EP chemotherapy. Methods: Patients who received 3 cycles of EP120 chemotherapy (50mg/m2 cisplatin day 1 and 2 and 120mg/m2 etoposide days 1, 2 and 3 every 3 weeks for 3 cycles) for stage 2 or stage 3 seminoma between 01/03/2000 and 31/05/2015 were identified. Data were retrospectively collected on stage, prognostic group, previous adjuvant treatment, serological and radiological response, time to relapse and subsequent management, progression-free survival (PFS) and overall survival (OS). Results: We identified 115 patients who received EP120 for seminoma and who met the inclusion criteria. Median age was 40 years (range 17-72). All patients were in the good-prognosis group. 103 patients (90%) were diagnosed with stage 2 seminoma, 12 patients (10%) with stage 3 (3 patients stage 3a and 9 stage 3b). 97 patients (84%) presented with stage 2 or 3 seminoma and 18 patients (16%) had progressed to stage 2 or 3 following adjuvant radiotherapy or adjuvant carboplatin chemotherapy for stage 1 disease. Seven patients (6%) with stage 2 seminoma relapsed after EP120 chemotherapy: 2 patients ≤3 months and 5 patients ≥ 3 months. None of the patients with stage 3 disease has relapsed so far. Of the 7 patients who relapsed, 2 received radiotherapy, 4 received TIP (paclitaxel, ifosfamide, cisplatin) chemotherapy and 1 received a combination of TIP chemotherapy and radiotherapy. All patients who relapsed after EP120 are currently in remission. Two of the 115 patients (1.7%) died whilst in remission and of unrelated causes. The 5-year PFS was 94% and the OS was 98%. Conclusions: Our data suggest that patients treated with 3 cycles of EP120 had survival rates similar to patients treated with more aggressive chemotherapy regimens.

Maintenance Oral Etoposide Following First Line Cisplatin-Etoposide Chemotherapy in Locally Advanced and Metastatic Non-Small Cell Lung Cancer Patients

Maintenance Oral Etoposide Following First Line Cisplatin-Etoposide Chemotherapy in Locally Advanced and Metastatic Non-Small Cell Lung Cancer Patients

Elevated serum soluble programmed cell death ligand 1 concentration as a potential marker for poor prognosis in small cell lung cancer patients with chemotherapy

BackgroundPotential relationship between serum soluble programmed cell death ligand 1 and prognosis of small cell lung cancer is not well explored. The aim of the study was to reveal the prognostic significance of serum soluble programmed cell death ligand 1 in patients with small cell lung cancer.MethodsA total of 250 small cell lung cancer patients and 250 controls were included. Research information was obtained from their medical records. Blood samples were collected on admission. Serum concentration of programmed cell death ligand 1 was measured using Enzyme-Linked Immunosorbent Assay. The patients underwent cisplatin-etoposide chemotherapy with a maximum of six cycles. Subsequently, they were followed-up for 12 months, and therapeutic response and cancer death were recorded.ResultsSerum concentration of programmed cell death ligand 1 was higher in the patients than in the controls on admission (P < 0.001). After chemotherapy, 112 patients had no response to this therapy. In the 12-month follow up period, 118 patients died due to this cancer. Multivariate Cox regression model revealed that the higher serum concentration of programmed cell death ligand 1 on admission was associated with the higher risk of no response to chemotherapy or cancer caused death (HR: 1.40, 95% CI: 1.05 ~ 1.87; HR: 1.43, 95% CI: 1.08 ~ 1.87).ConclusionElevated serum concentration of soluble programmed cell death ligand 1 might be an independent risk factor for non-response to chemotherapy and cancer caused death in small cell lung cancer patients.

Effects of thoracic radiotherapy timing and duration on progression-free survival in limited-stage small cell lung cancer.

Concurrent chemoradiotherapy (CRT) has been recommended and applied widely as the standard treatment for limited‐stage small cell lung cancer (LS‐SCLC). However, controversies remain regarding the optimal timing and treatment duration of thoracic radiotherapy (TRT), and their effects on patient survival. To evaluate prognostic values of TRT timing and duration on progression‐free survival (PFS) in LS‐SCLC and their dependence on TRT fractionation and clinicopathological characteristics, we retrospectively analyzed 197 LS‐SCLC patients receiving CRT from 2000 to 2016 at Sun Yat‐sen University Cancer Center. Based on the optimal cut‐off values of TRT timing and duration generated by Cutoff Finder, patients were divided into early TRT/late TRT group and short TRT/long TRT group respectively. Univariate and multivariate Cox analysis were performed to assess correlations of TRT timing, duration, fractionation, and clinicopathological characteristics with PFS. Univariate analysis revealed that early‐initiated TRT (P = 2.54 × 10−4) and short TRT (P = .001) significantly correlated with longer PFS. Their PFS benefits persisted in patients receiving hyperfractionated TRT and etoposide‐cisplatin (EP) chemotherapy, but were less prominent in those receiving once‐daily TRT and non‐EP chemotherapy. Multivariate analysis further identified early initiated TRT (P = .004) and short TRT (P = .017) as independent prognostic factors for longer PFS in LS‐SCLC. Our study confirmed that early‐initiated TRT and short TRT had positive prognostic roles in LS‐SCLC, especially in patients receiving hyperfractionated TRT and etoposide‐cisplatin chemotherapy. TRT fractionation was not an independent prognostic factor in LS‐SCLC.

Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial

SummaryBackgroundConcurrent chemoradiotherapy is the standard of care in limited-stage small-cell lung cancer, but the optimal radiotherapy schedule and dose remains controversial. The aim of this study was to establish a standard chemoradiotherapy treatment regimen in limited-stage small-cell lung cancer.MethodsThe CONVERT trial was an open-label, phase 3, randomised superiority trial. We enrolled adult patients (aged ≥18 years) who had cytologically or histologically confirmed limited-stage small-cell lung cancer, Eastern Cooperative Oncology Group performance status of 0–2, and adequate pulmonary function. Patients were recruited from 73 centres in eight countries. Patients were randomly assigned to receive either 45 Gy radiotherapy in 30 twice-daily fractions of 1·5 Gy over 19 days, or 66 Gy in 33 once-daily fractions of 2 Gy over 45 days, starting on day 22 after commencing cisplatin–etoposide chemotherapy (given as four to six cycles every 3 weeks in both groups). The allocation method used was minimisation with a random element, stratified by institution, planned number of chemotherapy cycles, and performance status. Treatment group assignments were not masked. The primary endpoint was overall survival, defined as time from randomisation until death from any cause, analysed by modified intention-to-treat. A 12% higher overall survival at 2 years in the once-daily group versus the twice-daily group was considered to be clinically significant to show superiority of the once-daily regimen. The study is registered with ClinicalTrials.gov (NCT00433563) and is currently in follow-up.FindingsBetween April 7, 2008, and Nov 29, 2013, 547 patients were enrolled and randomly assigned to receive twice-daily concurrent chemoradiotherapy (274 patients) or once-daily concurrent chemoradiotherapy (273 patients). Four patients (one in the twice-daily group and three in the once-daily group) did not return their case report forms and were lost to follow-up; these patients were not included in our analyses. At a median follow-up of 45 months (IQR 35–58), median overall survival was 30 months (95% CI 24–34) in the twice-daily group versus 25 months (21–31) in the once-daily group (hazard ratio for death in the once daily group 1·18 [95% CI 0·95–1·45]; p=0·14). 2-year overall survival was 56% (95% CI 50–62) in the twice-daily group and 51% (45–57) in the once-daily group (absolute difference between the treatment groups 5·3% [95% CI −3·2% to 13·7%]). The most common grade 3–4 adverse event in patients evaluated for chemotherapy toxicity was neutropenia (197 [74%] of 266 patients in the twice-daily group vs 170 [65%] of 263 in the once-daily group). Most toxicities were similar between the groups, except there was significantly more grade 4 neutropenia with twice-daily radiotherapy (129 [49%] vs 101 [38%]; p=0·05). In patients assessed for radiotherapy toxicity, was no difference in grade 3–4 oesophagitis between the groups (47 [19%] of 254 patients in the twice-daily group vs 47 [19%] of 246 in the once-daily group; p=0·85) and grade 3–4 radiation pneumonitis (4 [3%] of 254 vs 4 [2%] of 246; p=0·70). 11 patients died from treatment-related causes (three in the twice-daily group and eight in the once-daily group).InterpretationSurvival outcomes did not differ between twice-daily and once-daily concurrent chemoradiotherapy in patients with limited-stage small-cell lung cancer, and toxicity was similar and lower than expected with both regimens. Since the trial was designed to show superiority of once-daily radiotherapy and was not powered to show equivalence, the implication is that twice-daily radiotherapy should continue to be considered the standard of care in this setting.FundingCancer Research UK (Clinical Trials Awards and Advisory Committee), French Ministry of Health, Canadian Cancer Society Research Institute, European Organisation for Research and Treatment of Cancer (Cancer Research Fund, Lung Cancer, and Radiation Oncology Groups).

Synchronous Adie's syndrome and type 1 antineuronal nuclear antibody (anti-Hu)-related paraneoplastic neurological syndromes as predictors of complete response in limited-stage small-cell lung cancer: A case report.

Adie's syndrome (AS) and paraneoplastic sensorimotor neuropathy with cerebellar ataxia (PSN CA) are extremely rare, rapidly progressive, autoimmune diseases associated with the development of antibodies against neuronal-specific Hu proteins that are abnormally expressed in small-cell lung cancer (SCLC). We herein present the unique case of a 55-year-old obese woman, previous heavy smoker, who, during treatment with standard cisplatin-etoposide chemotherapy for limited-stage SCLC, developed simultaneous AS and worsening symptoms consistent with PSN CA that led to significant neurological disability and severe axonal electrophysiological pattern on nerve conduction studies. Serology confirmed the presence of low-titre type 1 antineuronal nuclear antibodies (ANNA-1), previously referred to as anti-Hu antibodies. Following plasmapheresis, immunosuppressive therapy and physical rehabilitation, the neurological symptoms progressively improved. The tumour completely regressed, with no recurrence detected on subsequent radiological examinations. The aim of this case was to highlight the importance of a multidisciplinary team approach for early recognition and rapid treatment of paraneoplastic neurological syndromes (PNS) as key to achieving significant recovery and marked improvement of the neurological deficit. This report extends the literature by confirming earlier studies showing that the presence of serum ANNA-1 in SCLC, an aggressive type of pulmonary carcinoma that is challenging to treat, may portend a more favourable prognosis and response to chemotherapy. Thus, patients with SCLC and new-onset neurological symptoms should be tested for ANNA-1. The role of a multimodality approach to treating PNS is also emphasized.

Etomidate as an emergency treatment for uncontrolled hypercortisolism in metastatic adrenocortical carcinoma

Adrenocortical carcinoma is a rare malignancy of poor prognosis with frequent excessive secretion of cortisol or androgens or both. The treatment could be challenging, especially in advanced or metastatic cases. We present the case of a 26-year-old woman with a multiple metastatic adrenocortical carcinoma. A few months prior to diagnosis, she developed clinical signs of virilization and a Cushing's syndrome. Mitotane and ketoconazole combination therapy was initiated after histopathological confirmation. A surgical resection of the left adrenal gland was performed. The tumor was classified pT2Nx (score Weiss 9, Ki67 10%). Cisplatin-Etoposide chemotherapy was started 20 days postoperatively. In the presence of persistent severe and life-threatening hypercortisolism (Urinary free cortisol [UFC] > 20-fold the upper limit of the normal range [ULN]), adding metyrapone was indicated but this drug is not available in Belgium. An alternative urgent treatment with etomidate (0.3 mg/kg/hour) by continuous intravenous infusion was administrated for 24 hours. The inhibition of the adrenal cortisol production was rapid prompting a need for a substitution by hydrocortisone (8 hours after treatment initiation). UFC decreased to less than 5-fold the ULN. One month later, the medical evaluation shows normalized UFC and regression of metastasis after 2 cycles of chemotherapy. Etomidate, mostly known as anesthetic, is a strong enzymatic inhibitor of the 11β-hydroxylase implicated in the last step of the adrenal cortisol steroidogenesis. There are only limited data on its use in severe hypercortisolism. This case illustrates its utility and efficacy in acute phase of hypercortisolism while waiting for action of other adrenal-directed therapies.

Treatment of advanced seminoma with 3 cycles of etoposide-cisplatin chemotherapy (EP120): A single-centre retrospective cohort study.

e16046Background: More than 95% of patients diagnosed with advanced seminoma are cured with chemotherapy - either 3 cycles of bleomycin (B), etoposide (E) and cisplatin (P) or 4 cycles of E-P. Radiotherapy can also be used for low-volume (Stage IIA-B) metastatic disease but may be associated with a higher risk of secondary malignancy. There is increasing emphasis on minimising late treatment toxicity in chemo-curable cancers. The optimal regimen to achieve long-term survival with minimal toxicity in advanced seminoma remains uncertain, in particular the value of bleomycin. Methods: Patients with advanced (Stage IIA and above) pure seminoma treated with etoposide 120mg/m2 days 1,2 and 3 and cisplatin 50mg/m2 day 1 and 2 (EP120) every 3 weeks for 3 cycles between the years 2000 and 2015 were retrospectively identified. Demographics, stage, clinical response, time of relapse, subsequent treatments and overall survival were recorded. Results: 117 patients were identified with a median age of 41years, and 15% ...

Pure Immature Teratoma of the Ovary in Adults: Thirty-Year Experience of a Single Tertiary Care Center.

ObjectiveThe aim of this study was to evaluate clinicopathologic characteristics, treatment outcome, and reproductive function in women diagnosed with ovarian immature teratoma (IT). Our standard chemotherapy regime is currently etoposide/cisplatin (EP), creating a unique opportunity to evaluate this protocol in ovarian ITs.Materials and MethodsThis study is a retrospective analysis. Twenty-seven women older than 18 years with ovarian IT stages IA to IIIC were identified and included in this study. Patients were treated at 1 institution, Health Sciences Center, Women’s Hospital, Winnipeg, Manitoba, Canada, between 1983 and 2013.ResultsThe median age at diagnosis was 27.0 years (range, 18–36 years). Twenty-two (82%) presented with an International Federation of Gynecology and Obstetrics stage I disease, 3 (11%) had stage II, and 2 patients (7%) had stage III disease. The histologic grade distribution was grade I in 9 patients (33%), grade II in 3 patients (11%), and grade III in 15 patients (56%). Initial management was surgical for all patients: 3 (11%) hysterectomy and bilateral salpingo-oophorectomy, 1 (4%) cystectomy only, and 23 (85%) unilateral salpingo-oophorectomy. Twenty-one patients (78%) received adjuvant therapy. The median follow-up was 60 months (range, 36–72 months). One patient recurred (histological grade III) 6 months after surgery and had a complete clinical response to 4 cycles of EP chemotherapy. Twelve patients reported an attempt to conceive resulting in 10 pregnancies (8 after chemotherapy).ConclusionsOvarian IT is a curable disease. Fertility-sparing surgery should be offered. Adjuvant treatment with cisplatinum-based chemotherapy, typically with bleomycin, etoposide, and cisplatin, is still considered the standard in stages greater than stage IA grade I. Etoposide/cisplatin as a primary chemotherapy regime for early- or advanced-stage disease is an effective treatment with minimal adverse effects and high tolerability. This is the first published study examining EP as a primary treatment modality for IT. Further studies are needed to strengthen these findings.