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This is a case of a young woman who developed neurological and psychiatric symptoms 3 days after resection of an immature teratoma. She was diagnosed with anti-NMDA receptor encephalitis via positive serum antibody titres, which was later confirmed with cerebrospinal fluid antibody titres. Given her cancer diagnosis, she underwent treatment with bleomycin, etoposide and cisplatin chemotherapy in addition to 5 days of high-dose steroids (1 g of intravenous methylprednisolone) for the encephalitis. This treatment regimen led to significant clinical improvement 3 weeks after completion of one cycle of chemotherapy.

A 37-year-old woman presented with a few days’ history of lower abdominal pain and an incidental finding of hypercalcaemia. A thorough workup ensued, and the cause was found to be an exceptionally rare ovarian tumour—ovarian small cell carcinoma of the hypercalcaemic type. Acute treatment of hypercalcaemia consisted of aggressive intravenous fluids and bisphosphonates. She underwent surgery to remove the tumour and is currently receiving systemic platinum/etoposide chemotherapy combination to be followed by pelvic radiotherapy. This case highlights the wide range of differential diagnosis for hypercalcaemia and the importance of a stepwise and thorough approach during investigations. We discuss the pathophysiology of malignancy-related hypercalcaemia, focusing especially on parathyroid hormone-related peptide-associated hypercalcaemia.

Non-Hodgkin’s lymphoma (NHL) presenting as a soft tissue sarcoma is rare, occurring at a rate of 0.11%. Peripheral T-cell lymphomas comprise 4% of all NHLs. We report the case of a 49-year-old Caucasian man who presented with a mass in the medial aspect of the thigh. Ultrasound showed a complex subcutaneous mass. MRI demonstrated a superficial complex skeletal mass affecting the sartorius muscle with other lesions involving the femur and the gluteus maximus. Positron emission tomography-computed tomography (PET-CT) showed diffuse pulmonary metastases with no involvement of nodes, liver, spleen with high suspicion of advanced sarcoma. Core biopsy revealed a T-cell NHL, and staining was positive for anaplastic lymphoma kinase. The patient received six cycles of cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone. Repeat PET-CT showed reduction in the mass, with no fluorodeoxyglucose-avid uptake. Latest MRI showed near-normal intensity. Further PET-CTs determine disease remission or progression.

We report a case of a previously healthy woman in her early 70s who presented with 2 weeks of episodic abdominal pain and significant weight loss. Imaging of her abdomen revealed acute right ovarian torsion associated with bilateral ovarian enlargement and an indeterminant pelvic mass. An urgent laparoscopic bilateral oophorectomy was performed with pathological results consistent with triple-hit high-grade B-cell lymphoma. She was successfully treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab, intrathecal methotrexate and venetoclax with complete remission after three cycles. Ovarian lymphoma is a rare entity and its genetic features have not been well described. We performed a literature review, describe the current knowledge regarding ovarian lymphoma and its therapeutic implication in the genomic age.

Background Extragonadal yolk sac tumors (YSTs) occurring in the uterus are extremely rare. To report a uterine YST case in a prepubertal girl and review literature on uterine YST to outline clinical management in diagnosis and treatment. Case We present a case of a 2-year-old girl who presented with vaginal bleeding and a pelvic mass. The diagnosis of YST was confirmed via biopsy. After four cycles of neoadjuvant chemotherapy combined with cisplatin, etoposide, and bleomycin (PEB), vaginoscopic examination and laparoscopy revealed a uterine YST without metastasis. The patient was treated with laparoscopic hysterectomy and two cycles of PEB postoperatively. During the 18 months of follow-up, the patient remained disease-free. Summary and Conclusion Primary uterine YST is extremely rare and no treatment guidelines have been established to date. Surgery combined with PEB chemotherapy is considered effective for uterine YST.

Little is known about the safety and efficacy of delivering radiation therapy (RT) with concurrent DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) chemotherapy in patients with multiple myeloma. In this study, DCEP plus RT was safe, with low rates of grade 3+ hematologic toxicity and grade 2+ RT-related events. It was also effective at alleviating pain at symptomatic sites of disease and producing a radiographic response on imaging. INTRODUCTION: The concurrent delivery of radiation therapy (RT) with salvage chemotherapies in the management of relapsed and refractory multiple myeloma (MM) is an area of ongoing investigation. This study examined the safety and efficacy of palliative RT given in the setting of concurrent dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP). PATIENTS AND METHODS: Fifty-five patients with MM received RT to 64 different sites within three weeks of receiving DCEP from 2010 to 2020. A median dose of 20 Gray (range 8-32.5 Gy) was delivered in a median of 5 fractions (range 1-15). Patients received a median of 1 cycle (range 1-5) of DCEP. Rates of hematologic and RT toxicity were recorded along with pain, radiographic, and laboratory responses to treatment. RESULTS: RT was completed in 98% of patients. 21% of patients experienced RTOG grade 3+ hematologic toxicity before RT, which increased to 35% one-month post-RT (P = .13) before decreasing to 12% at 3 to 6 months (P = .02). The most common toxicity experienced was thrombocytopenia. Grade 1 to 2 non-hematologic RT-related toxicity was reported in 15% of patients while on treatment and fell to 6% one-month after completing RT. Pain resolved in 94% of patients with symptomatic lesions at baseline. Stable disease or better was observed in 34/39 (87%) of the targeted lesions on surveillance imaging. CONCLUSION: RT administered concurrently with DCEP was well-tolerated by most of the patients in this series, with low rates of hematologic and RT-related toxicity. RT was also very effective, with the vast majority of patients demonstrating resolution of their pain and a significant response on follow-up imaging.

Purpose Primary mediastinal B‐cell lymphoma (PMBCL) is a rare subtype of diffuse large B‐cell lymphoma (DLBCL). Despite its aggressive course, PMBCL is considered curable. While in recent years dose‐adjusted (DA) EPOCH‐R (rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) has become widely endorsed as first‐line therapy for newly‐diagnosed PMBCL, the optimal treatment for this disease and the role of radiotherapy (RT) remains unclear. DA‐EPOCH‐R provides good clinical outcomes, albeit is associated with short‐ and long‐term toxicity. To address this issue, the current retrospective bi‐icenter analysis compared efficacy and toxicity of DA‐EPOCH‐R and a less toxic R‐CHOP/R‐ICE regimen used for the treatment of newly‐diagnosed PMBCL. Patients and Methods The study included all patients with a histologically confirmed PMBCL diagnosis treated with DA‐EPOCH‐R or R‐CHOP/R‐ICE between 01/2013‐12/2020 at two tertiary medical centers. Patient demographic and clinical data were derived from institutional electronic medical records. The analysis included 56 patients: 31 received DA‐EPOCH‐R and 25 – R‐CHOP/R‐ICE. Results At a median follow‐up of 1.9 years (IQR 3.1 years), similar progression‐free survival (2.1 versus 2.4 years; p = 0.7667), overall survival (2.5 versus 2.7 years; p = 0.8047) and complete response (80%) were observed in both groups. However, DA‐EPOCH‐R was associated with significantly longer hospitalization required for its administration (p, Primary mediastinal B‐cell lymphoma (PMBCL) is a rare subtype of diffuse large B‐cell lymphoma that is considered curable despite its aggressive course. DA‐EPOCH‐R, widely employed as a first‐line therapy for newly diagnosed PMBCL, offers good clinical results, but its utility is hampered by high rates of short‐ and long‐term toxicity. Our findings suggest that the use of R‐CHOP/R‐ICE could be consider as an alternative to DA‐EPOCH‐R in PMBCL patients, since the former regimen, while providing similarly encouraging outcomes, is associated with lower toxicity and significantly reduced hospitalization.

Background Synovial sarcoma (SS) is characterized by local invasiveness and a propensity to develop distant metastases. Current treatment for pediatric patients is based on the strategy used by the two main international groups, the Children's Oncology Group (COG) and the European group (EpSSG). Overall survival (OS) and event free survival (EFS) vary according to different publications; however, they tend to be dismal in initially metastatic patients, as well as relapsed patients. Objective To describe the clinical, histopathological, molecular findings and outcome in a series of 22 pediatric patients treated at our institution over 15 years. Materials and methods A retrospective, descriptive study in patients with a histopathological or molecular diagnosis of SS between December 2005 and August 2019, treated according to the EpSSGNRSTS 2005 protocol. Results Median age at diagnosis was 138.1 months, 32.1% presented with a primary axial site, and 68% with a tumor larger than 5 cm. Initial metastatic disease was seen in 22.7%. Of initially localized patients, 70.6% were classified as high-risk. Chemotherapy was administered to 91% of our patients and 77.2% received radiotherapy. The 3-5- and 10-year OS and EFS was 66%, 58.7% and 48.9%, and 57%, 33%, 22.2% respectively. Localized patients had a 5- and 10-year OS of 73.3% and 61.1%, versus 40% and 0% in metastatic disease, respectively. The only statistically significant factors were presence of metastasis, tumor size and IRS group. Tumor relapse was seen in 31.8% of patients. Only patients with local recurrence that achieved a complete surgery are alive without disease. Treatment schemes after recurrence or progression included a combination of gemcitabine-docetaxel, vincristine-irinotecan-temozolomide, kinase tyrosine inhibitors, and metronomic therapy with cyclophosphamide or etoposide. A long progression free survival of 14 months was observed with etoposide. Conclusions Although the sample size was not large enough to draw robust conclusions, in our series, OS and EFS rates were found to be lower than those reported in other studies, probably related to unfavorable prognostic factors, including a high incidence of metastasis and tumors larger than 5 cm. New therapeutic strategies are needed to improve outcome, especially in metastatic and relapsed disease. In addition, assessing the role of maintenance therapy in larger numbers of patients and broadening the use of metronomic chemotherapy would be necessary.

Background The prognosis of high-risk osteosarcoma, defined by the presence of chemo-resistance, metastatic disease at diagnosis, and relapse, remains poor. The efficacy of high-dose chemotherapy (HDC) and autologous stem-cell transplantation (ASCT) for high-risk osteosarcoma is still unclear. Methods We retrospectively reviewed pediatric patients with high-risk osteosarcoma who underwent HDC and ASCT at our institution between 2002 and 2018 and performed a review of the literature regarding the efficacy of HDC and ASCT for high-risk osteosarcoma. Results Six patients with high-risk osteosarcoma underwent high-dose melphalan (180 mg/m2)-based chemotherapy followed by ASCT. Two patients received HDC consisting of ifosfamide and melphalan. Three patients received HDC consisting of etoposide, carboplatin, and melphalan. One patient underwent tandem HDC consisting of thiotepa and etoposide followed by melphalan, thiotepa, and etoposide. Non-hematological toxicities presented mainly as mucositis and diarrhea. Two patients developed grade 3 mucositis. No life-threatening toxicities were observed in any of the six patients. One patient with disease progression before HDC died of multiple metastases, while five patients, with no evidence of disease in the peri-transplant periods, were alive at the time of publication; there was no disease recurrence at a median follow-up period of 144 months (range, 24–215 months). Our review of the literature supports the use of HDC with a higher dose of melphalan (180–280 mg/m2) for high-risk osteosarcoma. Conclusions Melphalan-based HDC and ASCT can be a promising treatment for high-risk osteosarcoma. Additionally, surgical removal of macroscopic residual lesions may be essential in peri-transplant periods.

Purpose: To evaluate the clinicopathological characteristics and surgical outcomes in patients with pure ovarian immature teratomas (POITs). Materials and Methods: In this multicenter study, a retrospective review was made of the databases of six Gynecology Oncology Departments in Turkey to identify patients with POITs who had undergone surgery between 1993 and 2019. Results: Evaluation was made of 48 patients with a median age at diagnosis of 22.5 years (range, 15-37 years). In 40 (83%) patients, stage I was determined and in eight patients, an advanced stage (IIIB, IIIC, and IVB) was determined. Tumors were found to be grade I in 17 (35.4%) cases, grade II in 12 (25%), and grade III in 19 (39.6%). Fertility-sparing surgery was applied to 42 (87.5%) patients and radical surgery to 6 (12.5%). The median follow-up was 60 months (range, 3-246 months). Recurrence was seen in seven patients, all with grade III tumors. In the final pathological examination of recurrent tumors, mature teratoma was reported in five patients, and immature teratoma in one patient. Salvage surgery was not performed in one patient as the tumor was unresectable and so a regimen of bleomycin, etoposide, and cisplatin (BEP) was administered. Conclusion: POITs are rare tumors seen at a young age, and benign or malignant relapse can be seen in these tumors. In this cohort, the malignant recurrence rate was 4.1%, and the benign recurrence rate was 10.4%. All the recurrences were in grade III tumors. Benign recurrences can be treated with surgery alone and the malignant group should be treated with surgery followed by chemotherapy.

Early-stage natural killer/T-cell lymphoma (NK/TCL) patients usually receive a combination of chemotherapy and radiotherapy, but the optimal treatment approach has not yet been established. This study aimed to investigate the efficacy and safety profile of a novel chemotherapy regimen and sandwiched radiotherapy in early-stage NK/TCL. Patients with newly diagnosed stage IE/IIE disease were eligible. Patients were initially treated with two courses of the GELAD regimen (gemcitabine 1·0 g/m2 day 1, etoposide 60 mg/m2 days 1-3, pegaspargase 2000 units/m2 day 4, and dexamethasone 40 mg days 1-4), followed by intensity-modulated radiotherapy (IMRT; 50-56 Gy in 25-28 fractions) and two additional courses of GELAD chemotherapy. A total of 52 patients were enrolled. The overall response rate and complete response rate per Lugano 2014 criteria were 94·2% and 92·3% respectively. With a median follow-up of 32 months, the estimated four-year overall survival rate and progression-free survival rate were 94·2% [95% confidence interval (CI), 83·2% to 93·1%] and 90·4% (95% CI, 78·4% to 95·9%) respectively. The most common adverse events were related to pegaspargase. Haematological toxicities were mild, with grade 3/4 neutropenia in 15·4% of patients. Our study provides a new approach with high activity and improved safety for the treatment of early-stage NK/TCL patients. This study was registered at www.clinicaltrials.gov as NCT02733458.

PURPOSE A dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone plus rituximab (DA-EPOCH-R) regimen has been shown to deliver excellent survival for adults with primary mediastinal large B-cell lymphoma (PMLBL) without the use of radiotherapy. No international prospective evaluation of this regimen has previously been reported in children and adolescents. PATIENTS AND METHODS We conducted an international single-arm phase II trial involving patients younger than age 18 years with PMLBL who were to receive six courses of DA-EPOCH-R. The primary end point was event-free survival (EFS). Overall survival and toxicity were also assessed. This trial was registered (ClinicalTrials.gov identifier: NCT01516567 ). RESULTS Analyses were based on 46 patients. The median age was 15.4 years (interquartile range: 14-16 years). The median follow-up was 59.0 months (interquartile range: 52.6-69.2 months). Fourteen events were observed (eight relapses or progressions (including three parenchymal CNS relapses), four residual lymphoma, and two second malignancies). The 4-year EFS was 69.6% (95% CI, 55.2 to 80.9), which did not differ from the rate observed historically ( P = .59). Seven deaths occurred (six disease-related and one second malignancy). The overall survival was 84.8% (95% CI, 71.8 to 92.4). Twenty-two patients (48%) reached dose levels ≥ 4. Nonhematologic adverse events grade ≥ 3 or cardiac adverse events grade ≥ 2 occurred in 47 of 276 (17%) courses and 30 of 46 patients (65%). CONCLUSION DA-EPOCH-R did not improve the EFS compared with a historical control in this first prospective multisite international study of children and adolescents with PMLBL. Further studies are required to determine the optimum therapy for children and adolescents with this lymphoma.

Relapsed/refractory Primary Central Nervous System Lymphoma (R/R PCNSL) has a poor prognosis with no established preferred treatment. We report the efficacy and toxicity of a combination chemotherapy regimen: methotrexate, carmustine, etoposide, and prednisone with or without rituximab (RMBVP). This retrospective study included thirty patients who received a median of two 28-day cycles (0.5-5). The median age was 66 years (23-81); median KPS was 70 (30-90); 14 (46.7%) were women. Patients received a median of 2 prior lines of therapy and all received prior methotrexate. Of 29 evaluable patients, the overall response rate was 73.3% (n = 22). Median progression-free survival (PFS) was 15.6 months. Patients who recurred or progressed

Up to 20–40% of patients with Hodgkin’s lymphoma will eventually relapse after treatment, among which early relapse confers a poor outcome. With salvage chemotherapy followed by autologous stem cell transplantation (ASCT), the long-term remission rate is 30%. We report our experience of using a modified-BEAM conditioning regimen without BCNU consisting of etoposide, cytarabine, and melphalan (EAM) in a patient with relapsed Hodgkin’s lymphoma. Before transplantation, the patient achieved second complete remission (CR2) using brentuximab vedotin and ESHAP (BR-ESHAP) chemotherapy. The ASCT went well without significant complications. This case demonstrated the considerable efficacy of EAM protocol as a conditioning regimen in terms of sufficient ablative capabilities, and the patient showed a successful hematopoietic engraftment. Although durability of the disease-free survival needs further observation, it had nearly 18 months of complete remission and the patient was in good performance status at the time of writing this manuscript.

Background Germ cell tumors represent highly curable disease even in metastatic stage. However, poor-risk patients with an unfavorable serum tumor marker (STM) decline after the first cycle of chemotherapy represent a subgroup with dismal prognosis, with approximately 50% cure rate using bleomycin, etoposide, and cisplatin (BEP). Objective The aim of this study was to determine the efficacy and safety of paclitaxel, ifosfamide, and cisplatin (TIP) in this patient population. Design, setting, and participants This was an open-labeled, nonrandomized, single-center phase II trial to study the efficacy and toxicity of TIP in the first-line treatment of germ cell tumor patients with an unfavorable decline of STMs. Nineteen patients with a poor prognosis according to the International Germ Cell Cancer Collaboration Group classification and an unfavorable STM decline after the first cycle of chemotherapy were included in this phase II study (NCT02414685). The treatment regimen consisted of paclitaxel 250 mg/m2 on day 1, ifosfamide 1200 mg/m2 on days 1–5, and cisplatin 20 mg/m2 on days 1–5, totally for four cycles. Outcome measurements and statistical analysis The primary endpoint was complete response (CR) rate. An optimal Simon two-stage design was used with a type I error of 5% and study power of 80%. If fewer than six CRs to study therapy have been observed among the first 19 patients, the study was to be terminated. Results and limitations A CR was achieved in four (21.1%) patients; therefore, the study was terminated in the first stage. A favorable response rate (CR or partial remission with negative tumor markers) was observed in 14 (78.9%) patients. At a median follow-up period of 35.2 mo (range, 5.6–62.1 mo), ten (52.6%) patients experienced disease progression and eight patients (42.1%) died. The 2-yr progression-free and overall survival was 41.2% (95% confidence interval [CI] 16.8–65.7) and 72.7% (95% CI 48.9–96.4), respectively. TIP was well tolerated, and no unexpected toxicity was observed. No informative biomarkers, including miR-371a-3p was identified. Conclusions Treatment modification from the BEP to the TIP regimen in patients with an unfavorable STM decline after the first cycle of chemotherapy was not associated with improved outcome, and four cycles of BEP remain the standard treatment option in this patient population. Patient summary Poor-risk patients with an unfavorable serum tumor marker decline after the first cycle of chemotherapy represent a subgroup with dismal prognosis, with an approximately 50% cure rate using bleomycin, etoposide, and cisplatin (BEP). Treatment modification from the BEP regimen to the paclitaxel, ifosfamide, and cisplatin regimen in patients with an unfavorable serum tumor marker decline after the first cycle of chemotherapy was not associated with improved outcome, and four cycles of BEP remain the standard treatment option in this patient population., Take Home Message Poor-risk patients with an unfavorable serum tumor marker (STM) decline after the first cycle of chemotherapy represent a subgroup with dismal prognosis, with approximately 50% cure rate using bleomycin, etoposide, and cisplatin (BEP). The aim of this study was to determine the efficacy and safety of paclitaxel, ifosfamide, and cisplatin (TIP) in this patient population. Treatment modification from the BEP to the TIP regimen in this patient population was not associated with an improved outcome, and four cycles of BEP remain the standard treatment option in this group of patients.

Poorly differentiated pancreatic neuroendocrine carcinomas (NECs) are rare and aggressive malignancies with rapid disease progression and early widespread metastasis. Given histology similarity, they are commonly treated with platinum-based chemotherapy as small cell lung cancer (SCLC). However, no standard treatment has been established for recurrent or progressive disease. We present an Asian patient with recurrent poorly differentiated pancreatic NEC after curative surgery and adjuvant chemotherapy with cisplatin and etoposide. The tumor mutational burden (TMB) was high. The patient received chemotherapy combined with maintenance immunotherapy with nivolumab and achieved promising and durable response, suggesting TMB could be a biomarker to identify NEC patients for immune checkpoint inhibitor (ICI) treatment.

Durvalumab (IMFINZI®), a fully human monoclonal antibody against programmed cell death-ligand 1 (PD-L1), is approved for use in combination with etoposide and either carboplatin or cisplatin for the first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). In the pivotal phase III CASPIAN trial in previously untreated adults with ES-SCLC, the addition of durvalumab to chemotherapy for up to 4 cycles followed by maintenance durvalumab was associated with a significantly longer overall survival and a favourable hazard ratio for progression-free survival compared with chemotherapy alone for up to 6 cycles. A higher proportion of patients in the durvalumab plus chemotherapy group had an objective response compared with the chemotherapy alone group. The efficacy of durvalumab was also sustained with longer follow-up. Durvalumab in combination with etoposide and either carboplatin or cisplatin had a manageable tolerability profile in patients with ES-SCLC. Given the available evidence, durvalumab in combination with etoposide and either carboplatin or cisplatin represents a valuable treatment option for the first-line treatment of patients with ES-SCLC, and is an accepted standard of care option in this setting. Supplementary Information The online version contains supplementary material available at 10.1007/s11523-021-00843-0., Plain Language Summary Small cell lung cancer (SCLC) is the most aggressive form of lung cancer; extensive-stage (ES) disease, which accounts for about two-thirds of all SCLC, is associated with high relapse rates and a poor prognosis. Expression of programmed cell death-ligand 1 (PD-L1) on both tumour cells and tumour-associated immune cells is an adaptive immune response that helps tumour cells avoid detection and subsequent elimination by the immune system. Durvalumab (IMFINZI®) is a fully human monoclonal antibody against PD-L1, which blocks the interaction of PD-L1 with its receptors, thus enhancing anti-tumour immune responses. When used in combination with chemotherapy (etoposide and either carboplatin or cisplatin) in adults with untreated ES-SCLC, durvalumab prolonged overall survival compared with chemotherapy alone; the improvements in overall survival were also maintained with additional follow-up. The tolerability profile of durvalumab in combination with chemotherapy was manageable in patients with ES-SCLC. Durvalumab in combination with chemotherapy is an effective and valuable treatment option for previously untreated patients with ES-SCLC. Supplementary Information The online version contains supplementary material available at 10.1007/s11523-021-00843-0.

Background Dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) is a front-line treatment for patients with aggressive B-cell lymphomas. Bcl-2 is associated with chemoresistance due to BCL2 gene rearrangement or protein overexpression and is antagonised by venetoclax. We aimed to assess the safety of venetoclax with dose-adjusted EPOCH-R as initial therapy in aggressive B-cell lymphoma. Methods We conducted a single-arm, phase 1 study across seven treatment centres in the USA. Eligible patients were aged 18-80 years with histologically confirmed, previously untreated diffuse large B-cell lymphoma, transformed indolent non-Hodgkin lymphoma, high-grade B-cell lymphoma with double-hit or not otherwise specified, or primary mediastinal B-cell lymphoma, with Ann Arbor stage II-IV and Eastern Cooperative Oncology Group performance status of 0-2. Participants received six cycles of oral venetoclax 400 mg, 600 mg, or 800 mg once daily for 10 days per cycle with dose-adjusted EPOCH-R (one cycle every 3 weeks; baseline doses were intravenous rituximab 375 mg/m2 on day 1, intravenous etoposide 50 mg/m2 on days 1-4, oral prednisone 60 mg/m2 twice daily on days 1-5, intravenous vincristine 0·4 mg/m2 on days 1-4, intravenous cyclophosphamide 750 mg/m2 on day 5, and intravenous doxorubicin 10 mg/m2 on days 1-4). A subsequent cohort received venetoclax 600 mg once daily for 5 days per cycle. The primary endpoints were the maximum tolerated dose, dose-limiting toxicities, and the recommended phase 2 dose of venetoclax. Analyses were done per protocol. This trial is registered with ClinicalTrials.gov, NCT03036904, and enrolment is now closed. Findings Between Feb 3, 2017, and June 4, 2019, 34 patients were assessed for eligibility, and 30 were enrolled and received venetoclax with dose-adjusted EPOCH-R. The median patient age was 64·0 years (IQR 51·6-69·4). The maximum tolerated dose was 800 mg for 10 days and the established recommended phase 2 dose was 600 mg for 5 days due to tolerability for treatment duration. One (3%) of 30 patients had a dose-limiting toxicity in cycle one (grade 4 thrombocytopenia with 800 mg dose). The most common grade 3-4 adverse events were cytopenias (28 [93%] of 30 patients); febrile neutropenia occurred in 19 (63%) patients. Grade 3-4 non-haematological adverse events included hypophosphataemia (n=10), hypokalaemia (n=7), and hyperglycaemia (n=5). Serious adverse events included infection (n=7) and gastrointestinal toxicities including abdominal pain (n=3), colonic perforation (n=1), and small intestinal obstruction (n=1). There was one treatment-related death (sepsis). Overall response rate was 96·7% (95% CI 82·8-99·9); 28 (93·3% [77·9-99·2]) of 30 patients had complete response and one (3·3% [0·1-17·2]) had a partial response. Interpretation Venetoclax with dose-adjusted EPOCH-R showed an acceptable safety profile at the recommended phase 2 dose and had encouraging preliminary activity in this population at high risk of adverse outcomes, and is worthy of further study. The combination is being investigated in Alliance 051701 (NCT03984448). Funding Genentech.

While survival rates for patients with relapsed/refractory osteosarcoma are low, kinase inhibitors have shown efficacy in its treatment. The multikinase inhibitor lenvatinib, plus ifosfamide and etoposide, showed antitumor activity in a Phase II study in patients with relapsed/refractory osteosarcoma. This Phase II randomized controlled trial (OLIE) will assess whether the combination of lenvatinib + ifosfamide + etoposide is superior to ifosfamide + etoposide alone in children, adolescents and young adults with relapsed/refractory osteosarcoma. The primary end point is progression-free survival; secondary and exploratory end points include, but are not limited to, overall survival, objective response rate, safety and tolerability, pharmacokinetic characterization of lenvatinib in the combination treatment, quality of life and quantification of baseline unresectable lesions that are converted to resectable.Lay abstract Traditional treatment for osteosarcoma (bone cancer) includes drugs that cause cell damage, such as ifosfamide and etoposide. The study in this article looked at adding lenvatinib, a drug that works to block development of blood vessels, to traditional chemotherapy to see whether it worked better. ‘OLIE’ is a Phase II clinical study comparing lenvatinib + chemotherapy (ifosfamide + etoposide) to the chemotherapy alone (ifosfamide + etoposide). An earlier study indicated that this drug combination may be successful. The study includes children, adolescents and young adults with osteosarcoma that has come back after, or did not respond to, previous treatment. OLIE will look at the antitumor activity and the side effects of this drug combination. The OLIE study is currently enrolling patients worldwide.

Purpose To characterize and compare both the outcome and cost of treatment of outpatient (OP) and inpatient (IP) ifosfamide therapy. Methods A single-center retrospective chart review of patients 18 years and older receiving ifosfamide therapy. The primary endpoint compares and evaluates the side effect profiles of ifosfamide-treated patients in the OP/IP settings. The adverse event grading system was characterized using the CTCAE Version 5.0. The highest grade was documented per cycle. The secondary endpoint of this study compares the costs of OP/IP therapy. It was assumed that the cost of medication was equivalent for IP/OP treatments. The cost saved with OP administration was determined by the average cost of hospital stay for IP admission. Results Ifosfamide therapy of 86 patients (57 OP, 29 IP) was reviewed. The predominant OP regimens were doxorobucin-ifosfamide-mesna (AIM) with 43.9% and ifosfamide-etoposide (IE) with 29.8%. Grade 4 anemia, thrombocytopenia, and neutropenia were most frequent in IP vs OP therapies (22.9% IP vs 4.3% OP, 21.6% IP vs 9.2% OP, and 22.8% IP vs 19.6% OP respectively). Neutropenic fever (NF) occurred in 20 OP patients which were predominantly treated with AIM or IE and led to average hospital stay of 6 days. Neurotoxicity, treated with methylene blue (MB) occurred in 4 OP patients. OP therapy saved a total of 783 hospital days, leading to a cost savings of $2,103,921. Conclusions Transitioning ifosfamide to the OP setting is feasible for academic and community infusion centers with the OP administration being safe, well-tolerated, and associated with decreased total cost of care. The current processes allow for safe transition of chemotherapy of chemotherapy under times of COVID.

Background The majority of patients with small‐cell lung cancer (SCLC) show a good response in the early stages of treatment, but more than 90% of patients will develop drug resistance. Therefore, biomarkers are urgently needed to identify patients who can benefit from systemic treatment. Methods We prospectively enrolled 52 extensive‐stage SCLC patients before treatment from a local hospital to identify mutations related to patient prognosis, and verified them in the published Jiang's cohort and George's cohort. Results We found that patients with high mutations (mut‐high) in the fatty acid (FA) metabolism pathway had a longer progression‐free survival (PFS) in the local hospital cohort (HR = 0.446, 95% CI, 0.207–0.959, p = 0.0387) and a longer overall survival (OS) in Jiang's cohort (HR = 0.549, 95% CI, 0.314–0.960, p = 0.0351) than patients with low mutations (mut‐low). Multivariate analysis suggested that mut‐high status was an independent prognostic factor in both cohorts. George's cohort verified that mut‐high status was associated with a longer OS than mut‐low status (HR = 0.730, 95% CI 0.440–1.220, p = 0.2277). The possible mechanisms were as follows: the frequency of mutated FA synthase (FASN) in the mut‐high group was greater than that in the mut‐low group, and pathways related to the cell cycle, DNA repair, and oxidative phosphorylation were enriched in the mut‐high group. Conclusions The prognosis of SCLC patients treated with chemotherapy was better among patients with more mutations in the FA metabolism pathway, and the underlying mechanisms could be found at the genome and transcriptome levels., We prospectively enrolled 52 extensive‐stage SCLC patients before treatment from local hospital to identify mutations related to patient prognosis. We found that the patients with high mutations (mut‐high) in the fatty acid (FA) metabolism pathway had better prognosis in the local hospital cohort and the Jiang's cohort than patients with low mutations (mut‐low). Then it was verified in George's cohort that mut‐high status was associated with a longer OS than mut‐low status. Finally, the possible mechanisms were explored from the genome and transcriptome levels.

Introduction: This study was conducted to develop and validate a nomogram for predicting the risk of neutropenia or febrile neutropenia (FN) in tumor patients in the first cycle of etoposide-based chemotherapy. Methods: This retrospective cohort study used an information system to monitor patients with non-Hodgkin’s lymphoma or solid tumors receiving an etoposide regimen in the first chemotherapy cycle in our hospital from 2009 to 2020. Binary logistic regression analysis was used to identify the influencing factors of patients with neutropenia or FN. Those factors were then used to develop a nomogram. Results: A total of 1,554 patients were divided into the development group (n = 1,072) and validation group (n = 482). Variables used to predict neutropenia or FN were Karnofsky performance status (odds ratio [OR] = 0.85, 95% confidence interval [CI] = 0.81–0.89, p < 0.01), metastatic sites ≥3 (OR = 6.33, 95% CI = 2.66–15.11, p < 0.01), comorbidity of heart disease (OR = 4.88, 95% CI = 1.74–13.67, p < 0.01), recent surgery (OR = 7.96, 95% CI = 1.96–32.36, p < 0.01), administration of alkylating agents (OR = 4.50, 95% CI = 1.10–18.48, p < 0.01), total bilirubin ≥25 μmol/L (OR = 11.42, 95% CI = 4.00–32.61, p < 0.01), and lymphocyte count 9/L (OR = 4.22, 95% CI = 2.00–9.75, p < 0.01). Conclusion: This model can aid the early identification and screening of the potential risk of neutropenia or FN in the first cycle of treatment for patients using etoposide-based chemotherapy.

BACKGROUND Large Cell Neuroendocrine Carcinoma of the Lung (L-LCNEC) is a rare type of neuroendocrine lung cancer that is increasingly diagnosed. However, the optimal management regarding the advanced stage is unclear. The purpose of this article is to present and compare our experience when L-LCNEC is treated as Small Cell Lung Cancer (SCLC). PATIENTS AND METHODS Overall, eight cases of L-LCNEC were included. We retrospectively reviewed medical files and reports by accessing the Institution's Data of patients diagnosed with L-LCNEC from April 2019 until December 2020 and evaluated their response to the combination of Platinum - Etoposide - Atezolizumab as first-line chemotherapy. RESULTS The overall observed response rate (ORR) of 75%. The median PFS was 6.85 months. The median response duration was 5.5 months. CONCLUSIONS Comparing our findings with other retrospective and prospective studies, it seems that the systematic treatment of choice and management in L-LCNEC of the lung should be that of a small cell carcinoma of the lung.

Introduction. Over the past decades, a significantly greater understanding of the morphology and molecular biological characteristics of tumors of the Ewing sarcoma family (ESFT) has been achieved. More than 70 % of relapses occur within 2 years from the date of diagnosis. In about 2/3 of cases, relapse occurs in distant places; this type of relapse is especially common in patients who initially have metastases. On the contrary, isolated local metastasis most often (in 1/5 of cases) occurs in patients with a localized form of the disease. In half of the patients, a relapse of the disease was detected during a routine examination, was asymptomatic and was a chance find.Purpose of the study – to evaluate the effectiveness of anti-relapse treatment in patients with ESFT, to develop an algorithm for a personalized approach, to improve the results of overall and relapse-free survival in children and adolescents with ESFT.Materials and methods. Our study included patients with a confirmed diagnosis of Ewing sarcoma (ES), who received treatment from 2008 to 2019. The analysis of follow-up data was closed on 19.02.2021. The study included 274 patients aged 6 months to 18 years, the average age was 11.6 years. Up to 1 year in our study there were 2 children. Twelve (4.3 %) patients went out of follow-up within 2 to 9 months from the start of treatment; we did not include them in the subsequent analysis. Analyzed were 262 patients with ES who received treatment according to the protocols at the Research Institute of Pediatric Oncology and Hematology of the N.N. Blokhin National Medical Research Center of Oncology. A relapse of the disease was revealed in 48 (18.3 %) children out of 262 – the study group; 58 (22.1 %) patients showed disease progression during treatment. In 70.8 % (34/48) patients had an isolated relapse, in 14 (29.2 %) cases – a combined one. The defeat of only the lung tissue with a relapse of the disease occurred in 19/48 (39.6 %) cases, local relapse without metastasis – 7/48 (14.5 %) cases. In general metastatic lung disease occurred in 66.6 % of cases. The defeat of the brain and lymph nodes occurred in 4 %. Most of the patients were in the group from 11 to 17 years, inclusive – 38/48 patients, which amounted to 79 %. All 48 patients from the study group received anti-relapse therapy depending on the duration of the disease relapse. For late relapses the primary treatment regimen was used: alternating courses of chemotherapy with vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide. In early relapses two regimens were most used: vincristine/topotecan/cyclophosphamide and vincristine/irinotecan/temozolomide (VIT). The positive response rate with the antirelapse VIT regimen was 60 %, and the time to progression was 7.6 months. With the topotecan regimen the response rate was 45 % and the time to progression – 7 months.Results. The overall survival (OS) rate of patients when a relapse was detected was significantly (p £ 0.05) higher when compared with the group of patients who had progression of the disease, which is associated with the effect of anti-relapse chemotherapy. When analyzing OS of patients with ES it should be noted that the 5-year survival rate of all patients (n = 262) was 66.3 ± 3.3 %, compared with the group of patients with confirmed relapse (n = 48) – 53 ± 8.1 %. The median in the group of patients with relapse was 39.3 months. The follow-up time in the group with recurrent ES disease averaged 52.2 ± 32.3 months (from 12.6 to 142 months). OS of patients was analyzed depending on the interval of disease recurrence. The Interval No. 1 was from the beginning of the main treatment to the first relapse, with a median of 37.2 months. Interval No. 2 – from the date of the first relapse to the date of the second relapse with a follow-up time of 58.8 ± 29.1 months (from 28.6 to 108 months), the median was not reached. The second relapse occurred significantly less frequently than the first relapse (p = 0.000001).Conclusion. The outcome for patients with recurrent ES remains poor, and a standard approach to their treatment has not yet been established. Standard first and second lines chemotherapy can be effective in most patients in terms of reducing symptoms and increasing the time to further progression, but complete remission remains hard to reach. Further multidisciplinary study of prognostic factors, effects of various treatment regimens and protocols, study of the inclusion of targeted drugs in the therapy program is required.

Purpose Chemotherapy and concurrent thoracic radiation therapy (CCTRT) followed by prophylactic cranial irradiation (PCI) is the standard of care for limited-stage small cell lung cancer (LS-SCLC). We aimed to compare the efficacy and toxicity of moderately hypofractionated once-daily CCTRT with that of a standard twice-daily regimen. Methods and Materials This multicenter, phase 2, randomized study enrolled patients aged 18 to 75 years old who had pathologically confirmed LS-SCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Eligible patients received 4 to 6 cycles of etoposide-cisplatin chemotherapy and were randomized to receive twice-daily CCTRT at 45 Gray (Gy) in 30 fractions or once-daily CCTRT at 65 Gy in 26 fractions, commencing with cycles 1 to 3 of chemotherapy. PCI was given to good responders. The primary endpoint was progression-free survival (PFS). Results The analyses included 182 patients, with 94 in the twice-daily group and 88 in the once-daily group. CCTRT started with cycle 3 of chemotherapy for most patients (80.2%). At a median follow-up of 24.3 months, the median PFS was 13.4 months (95% confidence interval [CI], 10.8-16.0) in the twice-daily group versus 17.2 months (95% CI, 11.8-22.6) in the once-daily group (P = .031), with 2-year PFS rates of 28.4% (95% CI, 18.2-38.6) and 42.3% (95% CI, 31.1-53.5), respectively. The estimated overall survival was 33.6 months in the twice-daily group versus 39.3 months in the once-daily group (P = .137). The median locoregional PFS was 23.9 months in the twice-daily group and was not reached in the once-daily group (P = .017). The incidences of most toxicities were similar in both groups, except for a higher incidence of ≥grade 3 acute lymphopenia in the once-daily group (71.7% vs 40.2% in the twice-daily group; P Conclusions Moderately hypofractionated, once-daily CCTRT showed improved PFS and similar toxicities compared with twice-daily CCTRT in LS-SCLC. This regimen should be evaluated for comparison in a phase 3 randomized trial.

Small-cell lung cancer (SCLC) is a high-grade neuroendocrine carcinoma, metastatic at the time of initial diagnosis in 70% of cases. Within the 30% of localised tumours only 5% of patients are eligible for surgical treatment according to the recommendations of learned societies. These recommendations are mainly based on old phase II and III randomised prospective trials and more recent registry studies. Surgical care is only possible within a multimodal treatment and essentially concerns small-sized tumours without involvement of hilar or mediastinal lymph nodes. As with non-small cell lung cancer (NSCLC), lobectomy with radical lymph node removal is the recommended procedure to achieve complete tumour resection. Patient selection for surgery includes age, performance status and comorbidity factors. Adjuvant chemotherapy combining Platinum salts and Etoposide for resected stage I tumours is recommended by ASCO, ACCP and NCCN. The precise sequence of neo-adjuvant or adjuvant treatments remains controversial because of the large heterogeneity in clinical practice reported in the studies and the context at the time of SCLC discovery. The 5-year survival rate of patients with early stage disease (pT1-2N0M0) treated by lobectomy and adjuvant chemotherapy is between 30% and 58%, which validates the primary place that surgery must have in these early forms. There is certainly little or even no place for such a therapeutic sequence in locally advanced stages (T3-T4 or N2). However, the stage heterogeneity, as in NSCLC, makes final conclusions difficult. In fact, some registry studies with pairing scores reported a median survival of more than 20 months in N2 SCLC. So, all files of SCLC must be evaluated in a multidisciplinary meeting in order to find the optimal solution for patients with rare and heterogeneous tumours.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of peripheral T-cell lymphoma that occurs most often in adolescents and young adults and is rare in children. Because of the aggressive clinical course, resistance to conventional chemotherapy and poor prognosis of HSTCL, an effective treatment has not been established. We report the case of a 3-year-old girl with HSTCL presenting with trilineage myelodysplasia. Although the HSTCL was refractory to conventional chemotherapy, remission was achieved with salvage chemotherapy that included fludarabine and cytarabine, which were shown to be effective in the drug sensitivity assay. After undergoing umbilical cord blood transplantation with a conditioning regimen consisting of etoposide, cyclophosphamide and total body irradiation, the patient has remained in complete remission for 8 years. Single-nucleotide polymorphism array analysis revealed heterozygous deletions of PAX5 (9p), ETV6 (12p) and homozygous deletions of CDKN2A (9p). Exome analysis showed a heterozygous nonsense c.2961C>G (p.Tyr987Ter) variant of the KMT2C gene. To improve the poor prognosis of HSTCL, the chemotherapeutic regimen can be selected for each patient on the basis of drug sensitivity and molecular genetic characteristics.

Patients with small-cell lung cancer (SCLC) have a dismal prognosis with limited overall survival (OS) despite a high response rate to chemotherapy. Recently, immune checkpoint inhibitors, combined with chemotherapy, as the first-line treatment for extensive-stage (ES)-SCLC have shown improvement in clinical outcomes. Real-world data from 68 Korean ES-SCLC patients, treated with atezolizumab, etoposide, and carboplatin at Yonsei Cancer Center between June 2019 and November 2020, were retrospectively analyzed to determine safety and efficacy using Cox regression analysis. The median follow-up was 11.6 months. The median progression-free survival was 4.6 months (95% confidence interval [CI] 4.0–5.2), and the median OS was 12.0 months (95% CI 7.4–16.6). Baseline bone metastasis, immune-related adverse events (IRAEs), and elevated LDH were related to OS (hazard ratio 2.18, 0.33, and 4.64; P = 0.05, 0.02, and 0.003, respectively). Among the 42 patients with disease progression, liver metastasis progression and baseline bone metastasis were associated with inferior OS, but without statistical significance (hazard ratio 2.47 and 1.97; P = 0.25 and 0.26, respectively). Overall, 61 (89.7%) patients experienced treatment-related adverse events (TRAEs), with hematologic toxicities as the most common grade 3–4 TRAEs. Twenty-two (32.4%) patients experienced IRAEs, with skin rash as the most common, and five (7.4%) patients had grade-3 IRAEs (pneumonitis, hyperglycemia, and aspartate aminotransferase elevation). Atezolizumab, combined with etoposide and carboplatin, showed efficacy and safety in our real-world data. Further studies are needed to predict the response to immunotherapy in SCLC.

Adrenocortical carcinoma (ACC) is a rare but aggressive disease that lacks definitive treatment. We aim to evaluate role of ASXL1 in ACC and exploit its therapeutic merits therein. We performed in silico reproduction of datasets of the Cancer Genome Atlas (TCGA), GDSC (Genomics of Drug Sensitivity in Cancer) and Human Protein Atlas using platforms of cBioPortal, UALCAN, NET-GE, GSEA and GEPIA. Validation in ACC was performed in tissue, in vitro and in vivo using the NCI-H295R and SW-13 cells. ASXL1 was gained in over 50% of ACC cases with its mRNA overexpressed in DNA gained cases. ASXL1 overexpression was associated with recurrence and worsened prognosis in ACC. ASXL1 gain was associated with resistance to etoposide, doxorubicin and cisplatin (EDP). ASXL1 expression was positively correlated with FSCN1 expression. Targeting ASXL1 significantly impaired fitness of ACC cells, which could be in part rescued by FSCN1 overexpression. Targeting FSCN1 however could not rescue resistance to EDP induced by ASXL1 overexpression. Targeting ASXL1 sensitized ACC cells to EDP regimen but constitutive ASXL3 overexpression in SW-13 cells could induce resistance upon prolonged treatment. Functional gain of ASXL1 was common in ACC and exerted pro-tumorigenic and chemoresistance role. Targeting ASXL1 hold promise to ACC treatment.

A 44-year-old man presented at our hospital to be evaluated for persistent fever and dyspnea. A chest computed tomography (CT) scan showed diffuse ground glass shadows and a left hilar tumor shadow. Upon further examination, he was found to have leukopenia, thrombocytopenia, and elevated lactate dehydrogenase and ferritin levels. He was diagnosed with both squamous cell lung carcinoma by a transbronchial lung biopsy and hemophagocytic syndrome by a bone marrow biopsy. After receiving treatment with dexamethasone and etoposide, the blood test abnormalities and performance status improved. Chemotherapy for lung cancer was initiated. He had a partial response after first-line chemotherapy and thereafter underwent left upper sleeve lobectomy.

Objective: To determine the clinicopathologic features and germline tumor protein p53 (TP53) mutation in children with adrenocortical carcinoma (ACC). Material and Methods: This was a retrospective study. From 2009 to 2018, children with ACC from King Chulalongkorn Memorial Hospital and Phramongkutklao Hospital were enrolled into the study. Clinical presentations and hormonal profiles were recorded. Mutation analyses of the TP53 gene were acquired using the next-generation-sequencing method which was performed for germline samples of all patients and the parents of those who tested positive. Result: Two males and six females with ACC were enrolled into this study. The median age at diagnosis was 25.5 months (range 10 to 67 months). All participants had virilization, either virilization only (n=3) or associated with Cushing (n=5). All participants had had surgery to completely remove all of the tumor and three participants had received adjuvant chemotherapy consisting of etoposide, doxorubicin, and cyclophosphamide. All participants had three different known mutations in the TP53 gene: c.1010G>A (p.R337H), c.916C>T (p.R306*) and c.743G>A (p.R248Q). Two of the three participants with TP53 mutations had pulmonary metastasis. One participant had wild-type TP53 and pulmonary recurrence occurred one year after diagnosis. The median follow-up time was 31 months (range 10 to 168 months. As of this writing, seven participants survived without evidence of recurrence. No second malignancy was found in all participants. One participant who had c.916C>T died of pulmonary metastasis 10 months after diagnosis. Conclusion: We successfully identified three different germline TP53 mutations in patients with ACC. Progression to pulmonary metastasis and recurrence were higher among participants with TP53 mutations. The treatment outcome of childhood ACC was good when surgery and adjuvant chemotherapy were used.

Peripheral T-cell lymphomas (PTCLs) are known to have an aggressive clinical course and grave prognosis. Several recommended first-line treatment regimens are available, but identification of the superior treatment remain elusive. We conducted a systematic review and meta-analysis to determine which study-level factors and group of regimens affect survival outcomes. The MEDLINE, Embase, and Cochrane databases were searched from inception to January 2021, and phase II or III clinical studies evaluating the efficacy of chemotherapy regimens were included. Random effects models were used to estimate 3-year overall survival rate, complete remission rate, and subgroup differences. Meta-regressions were carried out with adjustments for relevant covariates. Overall, 34 cohorts from 28 studies comprising 1424 PTCL patients were included in the pooled analysis. Chemotherapy regimens were divided into four groups: cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), CHOP plus etoposide, gemcitabine-based, and others. The pooled 3-year overall survival rate was 0.49 (95% confidence interval [CI] 0.43-0.54) for CHOP, 0.61 (95% CI 0.52-0.70) for CHOP plus etoposide, 0.39 (95% CI 0.30-0.47) for gemcitabine-based, and 0.61 (95% CI 0.44-0.78) for others. CHOP plus etoposide was significantly better than CHOP, with the latter used as a reference (coefficient of 0.11; p = 0.035), with adjustment for the proportion of International Prognostic Index score 4-5 in meta-regression analysis. Although grossly divided groups were pooled and analyzed, among four regimen groups for frontline PTCL treatment CHOP plus etoposide showed better survival than CHOP.

Introduction Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting DLL3, a Notch pathway ligand highly expressed on SCLC cells. Rova-T was evaluated alone or in combination with platinum-based chemotherapy (cisplatin or carboplatin combined with etoposide [CE]) in frontline treatment of extensive-stage SCLC. Methods One cycle of CE pre-enrollment was permitted (later mandated). The following four cohorts were enrolled: Rova-T monotherapy (0.3 mg/kg, every 6 [q6] wk × 2; cohort 1; n = 4); Rova-T induction (0.3 mg/kg, q6 wk × 2) followed by CE every 21 days (q21) × 4 (cohort 2; n = 5); Rova-T (0.1 or 0.2 mg/kg, q6 wk × 2) overlapping with CE q21 × 4 (cohort 3; n = 14); and Rova-T maintenance (0.3 mg/kg, q6 wk × 2) after CE q21 × 4 (cohort 4; n = 3). Results A total of 26 patients were dosed (cohort 3: 14; cohorts 1, 2, and 4 combined: 12). Median age was 66 years, and 73% had Eastern Cooperative Oncology Group performance status of 1. In cohort 3, seven patients (50%) had confirmed objective responses, with a median progression-free survival of 5.2 months and median overall survival of 10.3 months. Compared with cohorts 1, 2, and 4 combined, cohort 3 had lower frequency of some Rova-T–related adverse events of special interest, such as pleural effusion (0 versus 33%), pericardial effusion (0 versus 17%), ascites (0 versus 8%), peripheral edema (36% versus 42%), generalized edema (0 versus 8%), pneumonia (7% versus 25%), and hypoalbuminemia (0 versus 17%). Conclusions Lower Rova-T doses may be associated with lower incidence of some Rova-T–related adverse events of special interest. Rova-T 0.2 mg/kg plus CE (cohort 3) was tolerable; however, there was no clear efficacy benefit of adding Rova-T to CE.

Testicular germ cell tumor (TGCT) is highly chemo-sensitive cancer; however, there is no established treatment for TGCT relapsed after multiple chemotherapy. Although pembrolizumab showed durable stable disease in some patients, no reliable biomarker for predicting response is available. High microsatellite instability (MSI) is rare in chemo-naïve TGCT. We report a TGCT patient with a rapid response to pembrolizumab. A 34-year-old Japanese male diagnosed with advanced TGCT underwent PCR-based testing of the primary site; it did not reveal MSI. He relapsed after four chemotherapy regimens: bleomycin, etoposide and cisplatin; paclitaxel, ifosfamide and cisplatin; vinblastine, ifosfamide and cisplatin; and irinotecan+nedaplatin with a total of 20 treatment cycles. Chemotherapy was thus discontinued. Re-examination by a CT-guided needle biopsy for progressing retroperitoneal lymph node (RPLN) metastases showed MSI-high; pembrolizumab was initiated. After only two doses, the human chorionic gonadotropin level decreased from 6500 to

Background One cycle of adjuvant chemotherapy with bleomycin, etoposide and cisplatin (BEP) has shown superiority in recurrence-free survival over retroperitoneal lymph node dissection (RPLND) in patients with clinical stage (CS) I non-seminomatous germ cell tumours (NSGCTs) of the testis in the setting of a phase III trial. We report the recurrences and late toxicities of this study after 13 years of follow-up. Methods Questionnaires from 382 patients with CS I NSGCT treated with 1 cycle of adjuvant BEP (arm A) or RPLND + two cycles of adjuvant BEP in cases of pathological stage II disease (arm B) were evaluated regarding recurrences and late toxicity. Overall, information on recurrence status was available in 337 patients, and 170 questionnaires were evaluable for toxicity (arm A: 95; arm B: 75). Results With a median follow-up of 13.8 years (0–22), 3 patients (1.6%) in arm A and 16 patients (8.4%) in arm B experienced recurrence. The 15-year PFS in arm A/B was 99% (CI 96–100%)/92% (CI 89–99%) (p = 0.0049). The 15-year OS in arm A/B was 93% (CI 87–97%)/93% (CI 86–97%) (p = 0.83). Eight patients (4.2%) in arm A and four patients (2.1%) in arm B showed metachronous secondary testicular cancer (p = 0.26). Five patients (2.6%) in arm A and four patients (2.1%) in arm B developed other malignancies. Toxicities were not significantly different apart from retrograde ejaculation, which occurred more frequently after RPLND (10% versus 24%, p = 0.01). Conclusions With long-term observation, one cycle of BEP remains superior to RPLND in preventing recurrence and was tolerated without any clinically relevant long-term toxicities.

Adrenocortical carcinoma (ACC) is a rare and aggressive disease that is often diagnosed at an advanced stage. There is no standard treatment for metastatic ACC; EDP-M (etoposide, doxorubicin, and cisplatin plus mitotane) is one treatment option. A randomized controlled trial (FIRM-ACT) evaluating the efficacy of EDP-M showed progression-free survival (PFS) was 5.0 months, overall survival (OS) was 14.8 months, the response rate was 19%, and adrenal insufficiency occurred in 3.4% of patients. However, the efficacy and safety of this regimen in Asia are not fully reported. We retrospectively analyzed 43 patients diagnosed with metastatic ACC at the National Cancer Center Hospital between 1997 and 2020. We evaluated PFS, OS, and response in 17 patients who received EDP-M as first-line therapy. The median age at treatment initiation was 45 years (range 18–74). Eight patients (47%) had autonomous hormone production, including six patients with hypercortisolism. The best response of partial response and stable disease was seen in two (12%) and ten (59%) patients, respectively. The median PFS was 6.2 months [95% confidence interval (CI): 4.3–10.0]. The median OS was 15.4 months (95% CI 11.6–not reached). Three patients received only one cycle due to adverse effects associated with hypercortisolism. Grade 3/4 adverse events associated with adrenal insufficiency occurred in three (17%) cases, resulting in EDP-M discontinuation. The EDP-M regimen had similar PFS to that observed in FIRM-ACT. Adrenal insufficiency was more frequent in the current study, but this could be managed with supportive endocrinological care such as cortisol replacement.

Second-line treatment options for patients with relapsed, extensive-stage small cell lung cancer (ES-SCLC) are limited, and even with currently available treatments, prognosis remains poor. Until recently, topotecan (a topoisomerase I inhibitor) was the only drug approved by the United States (US) Food and Drug Administration (FDA) for the management of ES-SCLC following progression after first-line treatment with etoposide plus a platinum derivative (EP; carboplatin preferred). With the most recent approval of EP plus a programmed death ligand 1 (PD-L1) inhibitor, there are now more therapeutic options for managing ES-SCLC. A number of novel agents have emerging data for activity in relapsed ES-SCLC, and single-agent lurbinectedin (an alkylating drug and selective inhibitor of oncogenic transcription and DNA repair machinery in tumor cells) has conditional FDA approval for use in this patient population. Trilaciclib, a short-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor, has also been recently approved as a supportive intervention for use prior to an EP or a topotecan-containing regimen to diminish the incidence of chemotherapy-induced myelosuppression. The current review is based on a recent expert roundtable discussion and summarizes current therapeutic agents and emerging data on newer agents and biomarkers. It also provides evidence-based clinical considerations and a treatment decision tool for oncologists treating patients with relapsed ES-SCLC. This paper discusses the importance of various factors to consider when selecting a second-line treatment option, including prior first-line treatment, available second-line treatment options, tumor platinum sensitivity, and patient characteristics (such as performance status, comorbidities, and patient-expressed and perceived values).

Background Gastric stump cancer, also known as gastric remnant cancer (GRC), is one of the main complications of postgastrectomy syndrome, which usually occurs following Billroth II reconstruction. The predominant histological subtype of GRC is adenocarcinoma, whereas neuroendocrine carcinoma is relatively rare. In particular, there are few recently reported cases of mixed neuroendocrine carcinoma (MNEC) in the English literature. Here, we present an extremely rare case of MNEC of the gastric stump. Case summary A 59-year-old patient presented to our department owing to chronic constipation. He had undergone subtotal gastric resection 35 years prior to admission because of benign peptic ulcer. After admission, the patient underwent several tests, and gastroendoscopy showed evidence of Billroth II gastrectomy and local thickening of the gastric stump mucosa at the gastrojejunostomy site, with bile reflux; pathological biopsy revealed adenocarcinoma. He was then diagnosed with GRC and underwent total gastrectomy, D2 Lymphadenectomy, and esophagojejunal Roux-en-Y reconstruction. Histopathological examination of the specimen identified MNEC comprising MNEC (60%), adenocarcinoma (30%), and squamous cell carcinoma (10%). Postoperative adjuvant chemotherapy was initiated on September 17, 2020. Taxol plus cisplatin was administered for only one cycle because of severe liver function damage, and the regimen was changed to etoposide plus cisplatin on October 10, 2020 for five cycles. The patient recovered, with no recurrence after 6 mo of follow-up. Conclusion Gastric MNECs (GMNECs) is a rare type of GRC. This study presented the unusual occurrence of GMNEC in the gastric stump. This case will contribute to improvements in our understanding of the carcinogenesis, biology, pathology, and behavior of GMNEC and GRC.

Background: Pediatric acute myeloid leukemia (AML) is a challenging disease to treat in low- and middle-income countries (LMICs). Literature suggests that survival in LMICs is poorer compared with survival in high-income countries (HICs). Aims: This study evaluates the outcomes of Kenyan children with AML and the impact of sociodemographic and clinical characteristics on outcome. Methods and Results: A retrospective medical records study was performed at Moi Teaching and Referral Hospital (MTRH) in Eldoret, Kenya, between January 2010 and December 2018. Sociodemographic and clinical characteristics, and treatment outcomes were evaluated. Chemotherapy included two “3 + 7” induction courses with doxorubicin and cytarabine and two “3 + 5” consolidation courses with etoposide and cytarabine. Supportive care included antimicrobial prophylaxis with cotrimoxazole and fluconazole, and blood products, if available. Seventy-three children with AML were included. The median duration of symptoms before admission at MTRH was 1 month. The median time from admission at MTRH to diagnosis was 6 days and to the start of AML treatment 16 days. Out of the 55 children who were started on chemotherapy, 18 (33%) achieved complete remission, of whom 10 (56%) relapsed. The abandonment rate was 22% and the early death rate was 46%. The 2-year probabilities of event-free survival and overall survival were 4% and 7%, respectively. None of the sociodemographic and clinical characteristics were significantly associated with outcome. Conclusion: Survival of Kenyan children with AML is dismal and considerably lower compared with survival in HICs. Strategies to improve survival should be put in place including better supportive care, optimization of the treatment protocol, and reduction of the abandonment rate and time lag to diagnosis with sooner start of treatment.

Hemophagocytic lymphohistiocytosis (HHL), a severe hyperinflammatory syndrome caused by aberrant activation of macrophages and cytotoxic T cells, is clinically manifested as a febrile onset along with cytopenias, high ferritin serum level and splenomegaly. In adult patients, secondary causes of it should be looked for, such as autoimmune and infectious diseases and neoplasms. Prompt initiation of treatment is important due to the high mortality of this syndrome.A case of a 53-year-old patient diagnosed with HHL associated with T-cell lymphoma is presented as a sudden onset of several symptoms and signs of HHL, along with infectious complications.Results: Once the diagnosis of HHL was made, treatment with Etoposide and Dexamethasone was started, and with the diagnosis of T-cell lymphoma established, chemotherapy treatment with a CHOEP scheme was started, with a favorable initial evolution.As HHL is a rare entity associated with high mortality, initial suspicion must be high when facing an acute onset of fever, cytopenia and splenomegaly. Nonetheless, diagnosing HHL is challenging and often appear superimposed on multiple infectious diseases. The early initiation of treatmbent is important given the high mortality of this pathologyLa linfohistiocitosis hemofagocítica (LHH) es un síndrome hiperinflamatorio severo causado por activación aberrante de macrófagos y células T citotóxicas que se manifiesta clínicamente como un cuadro febril asociado a citopenias, hiperferritininemia y esplenomegalia. Ante su diagnóstico en adultos se deben buscar causas secundarias como neoplasias hematológicas. El inicio precoz del tratamiento es importante debido a su elevada mortalidad.Se presenta el caso de una paciente de 53 años de edad que se le realizó diagnóstico de LHH asociada a Linfoma de células T. La forma de presentación de dicho cuadro fue de manera abrupta con varios síntomas y signos de dicho síndrome, además de múltiples complicaciones infecciosas asociadas.Ante el diagnóstico inicial de LHH se inició tratamiento con etopósido y dexametasona, y al obtener el diagnóstico de Linfoma de células T, se instauró tratamiento quimioterápico con esquema de CHOEP, con evolución inicial favorable.La LHH es una entidad poco frecuente asociada a una elevada mortalidad, por lo que su índice de sospecha debe de ser elevado ante un cuadro clínico y analítico compatible. Sin embargo, su diagnóstico constituye un gran desafío clínico, pudiendo presentarse en algunas ocasiones superpuesto a cuadros infecciosos múltiples. El inicio precoz del tratamiento es importante debido a su alta mortalidad.

Introduction: Landscape of Extensive Stage (ES)-SCLC treatment has been largely unchanged over the years. Chemotherapy, mostly based on cisplatin and etoposide, remained the standard-of-care for patients with ES-SCLC, without any additional improvement in outcomes for almost 40 years. In this scenario, immune check points inhibitors have emerged marking a turning point in cancer treatment and more recently for SCLC.Areas covered: Aim of the paper is to discuss ICIs impact on ES-SCLC treatment algorithms, review current clinical trials and explore future perspectives.Expert opinion: A growing body of evidence supports ICI-containing regimens as a new mainstay of ES-SCLC treatment. Whether subgroups of SCLC patients may have greater survival benefits from ICIs treatment needs to be better defined. Understanding the impact of tumor microenvironment and identifying reliable predictive and/or prognostic biomarkers will be fundamental to move towards a personalized treatment approach leading to improved survival.

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is an uncommon condition characterized by abnormal, excessive immune activation resulting in severe cytopenias from an uncontrolled inflammatory response. It can be primary/ familial or secondary/sporadic. Infections, particularly viral infections are a common cause of secondary HLH. HLH due to Human monocytic ehrlichiosis (HME) is very rare, hence we are reporting our cases. Objective: To review cases of Ehrlichia-associated HLH at our institution and perform a literature review regarding this entity. Methods: We reviewed cases of Ehrlichia-associated HLH for the previous two years at our institution (Carilion Clinic). We then performed a review of the published literature on it, using Pubmed. Results: Over the past two years, five cases of Ehrlichia-associated HLH were diagnosed at our hospital. The average age of the patients was 67 years with predominantly males. All the patients were pancytopenic, and a majority had abnormal liver function tests. Diagnosis of ehrlichiosis was made by serum polymerase chain reaction (PCR) assay on blood. Patients had further testing done because of lack of clinical improvement. All patients had significantly elevated ferritin levels. Bone marrow biopsy samples of all patients showed findings of hemophagocytosis. All, but one, patients were treated with doxycycline and a combination of etoposide and dexamethasone. Three patients recovered while two died. On review of medical literature, we found a total of only 36 cases of Ehrlichia-associated HLH, including our five cases. There were 19 adults and 17 children. Both population groups showed varying degrees of pancytopenia. Splenomegaly was relatively uncommon, seen in less than one-third of the patients. Ferritin and triglyceride levels were routinely elevated. Bone marrow biopsy showing hemophagocytosis was the confirmatory test in all patients. A significant number of patients, both adults and children, required a combination of doxycycline and chemotherapy (etoposide and dexamethasone) to achieve clinical cure. Children had a better prognosis than adults, with one child and four adults succumbing to their illness. Conclusions: Ehrlichia-associated HLH is a rare but emerging disease entity. In endemic areas, a high degree of suspicion is required to diagnose ehrlichiosis and HLH resulting from it. Early diagnosis and prompt initiation of treatment for HLH is key to a favorable outcome.

Immunotherapy has been a revolutionary innovation in cancer therapy in recent years, but it is accompanied by various unique immune-related adverse events (irAEs). Among these irAEs, anaphylactic shock is very rare. Here, we report a case of a patient who developed anaphylactic shock after receiving one dose of atezolizumab. A 74-year-old male patient with small cell lung cancer experienced recurrence 10 years after surgery. After one cycle of treatment, the patient developed a grade 2 rash and recovered after receiving oral methylprednisolone tablets. In the second cycle, atezolizumab was discontinued. Then, the patient was scheduled to receive atezolizumab plus carboplatin and etoposide again after three weeks, but approximately three minutes after an intravenous infusion of atezolizumab, the patient developed signs and symptoms of anaphylactic shock, such as dyspnea, cold limbs, and loss of consciousness. At this point, the infusion was immediately stopped, and a normal saline infusion was administered. Meanwhile, ECG monitoring, supplemental humidified high-flow supplemental 100% oxygen, epinephrine, dopamine, hormone treatment with methylprednisolone, and other anti-shock treatments were carried out. For better recuperation, this patient was transferred to the intensive care unit for further treatment and was discharged two days later. Anaphylactic shock develops rapidly and is also a very severe complication. Prompt detection, diagnosis, and therapeutic intervention are the basics for survival.

Background. Lung cancer (LC) occupies a leading position among malignant tumors in the world, it accounts for 11.4% of the total malignant neoplasms. In 2020, there were 2 206 771 new cases of LC and 1 796 144 deaths worldwide. Among the histological variants, small cell LC (SCLC) has the most unfavorable outcomes. This variant is considered highly sensitive to chemotherapy. Despite some successes in the treatment of this disease, the results of treatment remain problematical. In recent years, the use of immune checkpoint inhibitors has provided significant control of the course of the disease. Aim. To show the efficacy of atezolizumab in combination with chemotherapy in patients with metastatic SCLC. Materials and methods. A 76-year-old patient with left lung cancer, IVA T4N3M1b, the right supraclavicular lymph node metastases, exudative pleuritis of the left lung was under observation. The histological investigation showed SCLC. Brain metastases were not detected. ECOG 0. Results. The patient was treated using atezolizumab 1200 mg in combination with carboplatin 5 AUC and etoposide 100 mg/m2 on days 1, 2, 3 for four cycles, followed by a maintenance therapy regimen with atezolizumab 1200 mg every 21 days. The patient received 21 injections during 14 months. The assessment of treatment effect was evaluated using combined 18F-fluorodeoxyglucose positron emission and X-ray computed tomography. As a result of the treatment, after 7 months, a complete clinical and morpho-metabolic regression of the tumor was reached, which persisted throughout the period of the treatment. Among the adverse events were detected grade 2 anemia and first-stage sensory neuropathy. No immune-related adverse events were observed. Conclusion. The addition of atezolizumab to etoposide + carboplatin as the first-line therapy for extensive-stage SCLC provides the long-term overall and disease-free survival with achieving the satisfactory quality of life in patients and acceptable drug tolerance.

Purpose: To compare outcomes between patients with relapsed follicular lymphoma who received a nonmyeloablative allogeneic stem cell transplant (alloSCT) and those who received an autologous transplant (autoSCT). Patients and Methods: We evaluated 194 patients with follicular lymphoma who received an alloSCT (n = 98) or autoSCT (n = 96) at MD Anderson Cancer Center (Houston, TX). The transplant type used was based on donor availability and by Medicare reimbursement guidelines. Patients who received an alloSCT were enrolled in four consecutive trials in which they received fludarabine, cyclophosphamide (or bendamustine), and rituximab conditioning. autoSCT patients received R-BEAM (rituximab, carmustine, etoposide, cytarabine, and melphalan). Results: The median follow-up of survivors was 108 months for the alloSCT group and 102 months for the autoSCT group. Overall survival was significantly better for patients who received an alloSCT compared with those who received an autoSCT (62% vs. 46%; P = 0.048). Similarly, progression-free survival rates were 52% in patients who received an alloSCT and 31% in those who received an autoSCT (P < 0.001), and the 8-year relapse rates were 11% and 43%, respectively (P < 0.0001). Only three patients in the alloSCT group relapsed beyond 3.5 years. In the alloSCT group, the rates for grade 2 to 4 acute graft-versus-host disease (GVHD), grade 3 to 4 acute GVHD, and extensive chronic GVHD were 22%, 9%, and 38%, respectively. In the autoSCT group, the 8-year incidence of secondary myelodysplasia was 11%. Nonrelapse mortality was similar between the two groups (15% vs. 11% at 8 years; P = 0.27). Conclusions: This study shows that alloSCT is curative and confers superior survival compared with autoSCT in patients with follicular lymphoma.