Pathological complete response to neoadjuvant tislelizumab plus chemotherapy in stage IIIB small cell lung cancer: A case report and literature review.

Immunotherapy plus chemotherapy has been approved for the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC, stage IV). Recently, the 2023 version of the National Comprehensive Cancer Network Guidelines recommended immunotherapy plus chemotherapy as the neoadjuvant regimen in patients with resectable non-small cell lung cancer (NSCLC). However, it is still unclear whether the combination regimen of immunotherapy plus chemotherapy is also beneficial for SCLC in the neoadjuvant context. Here, we report the case of a patient with stage IIIB SCLC who showed long-term survival and good tolerance to the neoadjuvant chemoimmunotherapy consisting of tislelizumab (an anti-PD-1 monoclonal antibody) plus etoposide-carboplatin. The patient achieved pathological complete response after receiving two cycles of neoadjuvant tislelizumab and chemotherapy followed by surgery. Two courses of post-operative tislelizumab and etoposide-carboplatin treatment were performed. The patient has survived for more than 23 months with no recurrence or metastases after neoadjuvant therapy. Multiplexed immunofluorescence and immunohistochemistry staining showed that the post-treatment specimens had remarkable immune cells infiltration, including CD3+ T cells, CD4+ T cells, and CD8+ T cells, which contrasted with very low levels of these cells in the pre-treatment samples. This study is, to the best of our knowledge, the first attempt to present the neoadjuvant chemoimmunotherapy of tislelizumab in combination with etoposide-carboplatin in SCLC. Our study suggested that neoadjuvant tislelizumab plus chemotherapy may facilitate radical resection and benefit patients with locally advanced (stage IIB-IIIC) SCLC.

Real-world efficacy of DA-EPOCH-R/HD-MTX regimen in CD5-positive diffuse large B cell lymphoma: a single-institute analysis.

CD5-positive diffuse large B cell lymphoma (CD5+ DLBCL) is a high-risk lymphoma type. Recently, the PEARL5 (a Phase II trial of DA-EPOCH and Rituximab with HD-MTX therapy for newly diagnosed DLBCL with CD5 expression) study demonstrated the efficacy of the DA-EPOCH-R (cyclophosphamide, etoposide, doxorubicin, vincristine, prednisone, and rituximab)/HD-MTX (high-dose methotrexate) regimen for CD5+ DLBCL. In this report, we revealed the impact of the DA-EPOCH-R/HD-MTX regimen on the clinical course of CD5+ DLBCL in the real-world. We retrospectively compared CD5+ and CD5- DLBCL patients diagnosed from January 2017 to December 2020 and analyzed their clinicopathological characteristics, treatment, and prognosis. There was no difference in age, sex, clinical stage, and cell of origin; however, the CD5-positive group had higher lactate dehydrogenase levels and a worse performance status than the CD5-negative group (p=0.00121 and p=0.0378, respectively). International prognostic index (IPI) was worse in the CD5-positive group than in the CD5-negative group (p=0.0498), but NCCN-IPI (National Comprehensive Cancer Network-IPI) was no different between the two groups. The CD5-positive group was more frequently treated with the DA-EPOCH-R/HD-MTX regimen than the CD5-negative group (p =0.001857). Complete remission rate and 1-year overall survival did not differ between the CD5-positive and -negative groups (90.0% vs 81.4%, p=0.853; 81.8% vs 76.9%, p=0.433). We conclude that the DA-EPOCH-R/HD-MTX regimen is effective for CD5+ DLBCL in this single institute analysis.

A single-beam of light priming the immune responses and boosting cancer photoimmunotherapy.

Mirroring the rapid clinical performance, immune checkpoint blockade (ICB) leads a remarkable clinical advance in combating cancer, but suffers poor response in most cancers. The low presence of tumor-infiltration lymphocytes and the poor immunogenicity in tumor microenvironment (TME) are the main factors hindering the effectiveness of ICB in the treatment of immunological "cold" tumors. Aiming at boosting immune response via TME modulation, we report a near-infrared laser-guided photoimmuno-strategy in which synergistic phototherapy, immune adjuvant, and ICB are integrated into one versatile nanoporphyrin platform. The prepared nanoporphyrins are self-assembled from purpurin18-lipids and have photodynamic/photothermal and immunomodulatory effects that can be tuned under a single laser irradiation, concomitant with fluorescence or MSOT imaging. In this work, the contributions of each component in the nanoporphyrin platform were specified. In particular, phototherapy-driven in situ tumor cell death provided abundant tumor-associated antigens to initiate immune responses. With the assist of spatiotemporally delivered immune adjuvant, phototherapy potentiated tumor immunogenicity, reprogrammed "cold" tumors into "hot" ones, and sensitized tumors to ICB therapy. Further combined with PD-L1 blockade, the photoimmune-strategy substantially stimulated tumor-specific immune-responses and long-term immunological memory against primary tumor, abscopal tumor as well as metastatic foci. Such single light-primed photoimmunotherapy offers a promising solution to overcome common hurdles in ICB treatment and can potentially be integrated into existing clinical practice.

Recurrence and new tumor development after frontline intravenous chemotherapy for retinoblastoma: Risk factors and treatment results.

PURPOSE: To evaluate the risk factors leading to recurrence and new tumor (NT) development in patients with retinoblastoma after intravenous chemotherapy (IVC) and to review the treatment outcomes. MATERIALS AND METHODS: The records of 166 retinoblastoma cases (having 246 affected eyes) who underwent six-cycle IVC (vincristine, etoposide, and carboplatin) as primary treatment between October 1999 and August 2020 were reviewed retrospectively. RESULTS: The mean ages at presentation were 9.0 (median: 8.0) and 9.2 (median: 8.5) months in cases with recurrence and NTs respectively. Recurrence was detected in 40 (16.3%) eyes, NTs in 29 (11.8%), and both recurrence/NTs in 24 (9.8%). The mean time elapsed till recurrence and NT was 10.7 months. Multivariable analysis showed that the factors predictive of recurrence were largest tumor base diameter (LTBD) >12 mm (p = 0.039) and presence of subretinal seeds at diagnosis (p = 0.043). Multivariable risk factors for the development of NTs were bilateral familial retinoblastoma (p = 0.001) and presence of subretinal seeds at diagnosis (p = 0.010). Mean follow-up was 80.1 (median: 72.5) months. By Kaplan-Meier analysis, the 1-, 3-, and 6-year recurrence and NT rates were 21.2%, 28.1%, and 28.7% and 14.9%, 22.6%, and 23.9% respectively. The most common treatment methods used for recurrent and/or NTs included cryotherapy, transpupillary thermotherapy, and intra-arterial chemotherapy. Enucleation was eventually required in 24/93 (25.8%) eyes. No patient developed metastasis. DISCUSSION: Development of recurrence and/or NT after IVC was noted in 38% of all retinoblastoma eyes. Bilateral familial disease, LTBD >12 mm, and presence of subretinal seeds at baseline were risk factors for recurrence and NTs in this study.

Post-treatment persistent alpha-fetoprotein elevation in a patient with testicular cancer.

BACKGROUND: Persistent alpha-fetoprotein elevation in a patient following orchiectomy and chemotherapy for non-seminomatous testicular germ cell tumor is a rare condition when persistence of the tumor and false positivity of tumor marker elevation has to be differentiated. This situation often leads to over-treatment and potential toxicity with adverse events which can be severe. CASE: A case of a patient with the abovementioned disease and course of treatment is presented. As no radiological signs of the disease were present and the level of alpha-fetoprotein was mild and stable, the tumor marker elevation was evaluated as false positive. Possible causes of the tumor marker elevation were identified as other serious diseases are known to cause such a false positivity. The level of alpha-fetoprotein remained unchanged despite alcohol abstinence and hepatoprotective treatment by silymarin. Hepatitis B and C serological tests were negative, and no other malignant tumor was identified. Finding of terminal ileum circular wall thickening and stratification with a reaction of surrounding visceral fat and lymph nodes persisting in CT scans suggests the presence of inflammatory bowel disease, possibly explaining the alpha-fetoprotein elevation. The patient has no evidence of the disease more than 14 months after the end of chemotherapy treatment with no change in the elevation of alpha-fetoprotein. CONCLUSION: After the treatment, when no other indication of testicular cancer than an elevated alpha-fetoprotein level is present, the patient should be managed by ongoing surveillance.

Prognostic value of lymphocyte-to-monocyte ratio and histone methyltransferase G9a histone methyltransferase in patients with double expression lymphoma: A retrospective observational study.

ABSTRACT: In patients with diffuse large B-cell lymphoma, MYC combined with Bcl2 and/or Bcl6-based protein expression is called double expression lymphoma (DEL). R-DA-EPOCH program chemotherapy is typically recommended because these patients often have a poor prognosis. Although numerous factors affect survival of patients with DEL, the roles of the tumor biomarker histone methyltransferase G9a (G9a) and the lymphocyte-to-monocyte ratio (LMR) are unknown.We performed a retrospective analysis of data from 51 patients. These patients were newly diagnosed with DEL and treated with R-DA-EPOCH at Taizhou People' s Hospital and Northern Jiangsu People's Hospital between June 2014 and December 2019. Receiver operator characteristic curve results were used to calculate the LMR cutoff value. We used an immunohistochemical analysis to examine G9a expression in DEL tissues. The Kaplan-Meier method was used to determine progression-free survival (PFS) and overall survival (OS) characteristics. Cox proportional-hazards models were constructed for univariate and multivariate analyses to examine the prognostic values of LMRs and G9a in patients with DEL.The cutoff value for LMR was 2.18. The 5-year PFS rate was 35.3%, and the 5-year OS rate was 39.2%. Patients with DEL with lower LMRs and who were G9a-positive predicted inferior PFS and OS. Univariate analysis revealed that patients with elevated LDH levels, high National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) scores, LMRs ≤2.18, and G9a-positive results had relatively poorer PFS and OS. The multivariate analysis revealed that LMRs ≤2.18 and a G9a-positive result were independent prognostic factors for PFS and OS in patients with DEL treated with R-DA-EPOCH.The study results suggested that peripheral blood LMRs were an important marker for evaluation of prognosis in patients with DEL. High expression of G9a was associated with worse outcomes, indicating that G9a may serve as a prognostic biomarker for patients with DEL who undergo R-DA-EPOCH program chemotherapy.

Chidamide combined with ibrutinib improved the prognosis of primary bone marrow diffuse large B cell lymphoma.

Primary bone marrow diffuse large B cell lymphoma (DLBCL) is an independent pathologic type with a poor prognosis when treated with standard chemoimmunotherapy. Generally, rituximab-based high-dose chemotherapy regimens such as dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) can be administered to young patients, followed by autologous stem cell transplantation. For elderly patients, the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) regimen is well tolerated, but it is an insufficient induction therapy for this group. Herein, we reported an elderly patient diagnosed with primary bone marrow DLBCL, germinal center B-cell-like subtype. Considering tolerance, the R-CHOP regimen was administered. However, his disease progressed after two treatment cycles. Then, the rituximab, gemcitabine, dexamethasone, cisplatin, lenalidomide regimen was administered, but the patient still experienced disease progression. Subsequently, the histone deacetylase (HDAC) inhibitor chidamide and Bruton's tyrosine kinase (BTK) inhibitor ibrutinib were concurrently administered, and the patient achieved complete remission. We found that the response of primary bone marrow DLBCL to chemotherapy was poorer than that of de novo DLBCL. High-dose chemotherapy regimens such as DA-EPOCH should be administered to young patients in combination with rituximab. For elderly patients, new targeted drugs such as HDAC and BTK inhibitors appear to produce favorable outcomes.

Risk Factors for Tumor Recurrence Following Primary Intravenous Chemotherapy (Chemoreduction) for Retinoblastoma in 869 Eyes of 551 Patients.

PURPOSE: To identify risk factors for retinoblastoma recurrence following chemoreduction. METHODS: This was a retrospective review of patients with retinoblastoma treated from 1994 to 2019 using chemoreduction with analysis for recurrence using Kaplan-Meier, Cox regression, and logistic regression. RESULTS: There were 869 eyes of 551 patients with retinoblastoma treated with chemoreduction. Follow-up in 556 eyes revealed main solid tumor recurrence (n = 355, 64%), subretinal seed recurrence (n = 244, 44%), vitreous seed recurrence (n = 162, 29%), and/or new tumor (n = 118, 21%) requiring management with focal therapy (transpupillary thermotherapy, cryotherapy) (n = 294, 53%), intra-arterial chemotherapy (n = 125, 22%), intravitreal chemotherapy (n = 36, 6%), plaque radiotherapy (n = 120, 22%), external beam radiotherapy (n = 57, 10%), and/or enucleation (n = 49, 9%). Of all recurrences, 62% were detected by 1 year, 86% by 2 years, 94% by 3 years, 98% by 5 years, 99% by 10 years, and 100% by 15 years. Risk factors for recurrence on multivariate analysis included younger patient age at presentation (odds ratio [OR] = 1.02 [1.00 to 1.04] per 1 month decrease, P = .02), greater International Classification of Retinoblastoma group (OR = 1.24 [1.05 to 1.47] per 1 more advanced group, P = .01), shorter tumor distance to optic disc (OR = 1.11 [1.01 to 1.21] per 1 mm decrease, P = .03), and presence of subretinal seeds (OR = 1.66 [1.09 to 2.53], P = .02). CONCLUSIONS: Retinoblastoma recurrence after chemoreduction is usually detected within the first 3 years following treatment. Younger patients with more advanced, posteriorly located tumors and subretinal seeds at presentation are at increased risk, but recurrence can often be managed with globe-sparing therapy. [J Pediatr Ophthalmol Strabismus. 2020;57(4):224-234.].

Adjuvant chemotherapy for patients with gastric neuroendocrine carcinomas or mixed adenoneuroendocrine carcinomas.

BACKGROUND: The aim of this study was to evaluate whether adjuvant chemotherapy is associated with improved survival in patients with resectable gastric neuroendocrine carcinomas (G-NECs) or mixed adenoneuroendocrine carcinomas (G-MANECs). METHODS: The study included patients with G-NECs or G-MANECs who underwent surgery in one of 21 centres in China between 2004 and 2016. Propensity score matching analysis was used to reduce selection bias, and overall survival (OS) in different treatment groups was estimated by the Kaplan-Meier method. RESULTS: In total, 804 patients with resectable G-NECs or G-MANECs were included, of whom 490 (60·9 per cent) received adjuvant chemotherapy. After propensity score matching, OS in the chemotherapy group was similar to that in the no-chemotherapy group. Among patients with G-NECs, survival in the fluorouracil (5-FU)-based chemotherapy group and the non-5-FU-based chemotherapy group was similar to that in the no-chemotherapy group. Similarly, etoposide plus cisplatin or irinotecan plus cisplatin was not associated with better OS in patients with G-NECs. Among patients with G-MANECs, OS in the non-5-FU-based chemotherapy group was worse than that in the no-chemotherapy group. Patients with G-MANECs did not have better OS when platinum-based chemotherapy was used. CONCLUSION: There was no survival benefit in patients who received adjuvant chemotherapy for G-NECs or G-MANECs.

ANTECEDENTES: El objetivo de este estudio fue evaluar si la quimioterapia adyuvante mejoraba la supervivencia en pacientes con carcinomas gástricos resecables neuroendocrinos (gastric neuroendocrine carcinomas, G-NECs) y carcinomas adenoneuroendocrinos mixtos (mixed adenoneuroendocrine carcinomas, G-MANECs). MÉTODOS: Se incluyeron pacientes con G-NECs y G-MANECs tratados quirúrgicamente en 21 centros en China entre 2004 y 2016. Se utilizó un análisis de emparejamiento por puntaje de propensión para reducir el sesgo de selección y el método de Kaplan-Meier para estimar la supervivencia global (overall survival, OS) de los pacientes en los diferentes grupos de tratamiento. RESULTADOS: En total, se incluyeron en el estudio 804 pacientes con G-NECs y G-MANECs resecables y 490 pacientes (60,9%) recibieron quimioterapia adyuvante. Después del emparejamiento por puntaje de propensión, la OS del grupo con quimioterapia fue similar a la del grupo sin quimioterapia. En los pacientes con G-NECs, la supervivencia en los grupos con quimioterapia basada en 5-FU (fluorouracilo) y de quimioterapia sin 5-FU fue similar a la del grupo sin quimioterapia. Asimismo, la combinación de etopósido y cisplatino o de irinotecán y cisplatino no se asoció con una mejor OS en pacientes con G-NECs. En pacientes con G-MANECs, la OS del grupo con quimioterapia sin 5-FU fue peor que la del grupo sin quimioterapia. Los pacientes con G-MANECs no presentaron una mejor OS cuando se administró quimioterapia basada en platinos. CONCLUSIÓN: La administración de quimioterapia adyuvante en pacientes con G-NECs y G-MANECs no mejoró la supervivencia.

A Case of Recurrent Peritoneal Cancer in Which an Antitumor Effect Was Obtained Using a Combination of Etoposide and a Chinese Herbal Medicine with Maintenance of Daily Life.

The patient was a 50-year-old multiparous female (gravida/para 4/2) who had divorced. She was followed up for 1 year and 5 months after completion of initial treatment for peritoneal cancer (preoperative chemotherapy + optimal surgery + chemotherapy). A gradual increase in the tumor marker CA125 occurred, and computed tomography and ultrasonography showed bilateral neck, left supraclavicular and right axillary lymphadenopathy. The patient wanted to continue her job. Therefore, she was treated with etoposide (25 mg) daily for 3 weeks and TJ-48 (juzen-taihoto, 7.5 g) daily for 4 weeks, and then followed up. After two weeks, swelling of lymph nodes had been reduced or eliminated and tumor marker CA125 was negative. The only adverse reaction was slight numbness and the patient continued to work while receiving the same drugs orally for 2 years and 8 months without any symptoms or recurrence. This case shows that a combination of etoposide and TJ-48 has an antitumor effect on recurrent progressive peritoneal cancer while allowing a patient to work and have a normal daily life.

How I treat breast implant-associated anaplastic large cell lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently described form of T-cell non-Hodgkin lymphoma now formally recognized by the World Health Organization classification of lymphoid neoplasms. The disease most often presents with a delayed seroma around the breast implant, almost exclusively with a textured surface, and manifests with breast pain, swelling or asymmetry, capsular contracture, but can also present with a breast mass, and lymph node involvement. The prognosis of BIA-ALCL is favorable compared with many other subtypes of systemic T-cell lymphoma; however, unlike other non-Hodgkin lymphomas, complete surgical excision for localized disease is an important part of the management of these patients. In this paper, we share our recommendations for a multidisciplinary team approach to the diagnosis, workup, and treatment of BIA-ALCL in line with consensus guidelines by the National Comprehensive Cancer Network.

Targeting sialic acid residues on lung cancer cells by inhalable boronic acid-decorated albumin nanocomposites for combined chemo/herbal therapy.

Etoposide (ETP), as a potential treatment for lung cancer, has limited application due to its poor solubility, and systemic side effects. In the current study, we propose inhalable boronate-targeted HSA nanocomposites for combined delivery of ETP and the herbal drug, berberine (BER) for localized therapy of lung cancer. First, ETP was pre-formulated as phospholipid complex (EPC) to enhance drug solubility and facilitate its encapsulation within the hydrophilic albumin nanoparticles (NPs). Second, EPC and BER were then co-loaded with high efficiency into HSA NPs as a synergistic therapy for lung cancer. The NPs displayed suitable size around 200 nm and sequential drug release pattern. Moreover, conjugation of aminophenylboronic acid (APBA) to HSA NPs resulted in enhanced cytotoxicity and internalization into A549 lung cancer cells, compared to non-targeted NPs or free drugs via binding to sialic acid residues over-expressed by cancer cells. Using mannitol as a spray-drying carrier, the developed inhalable nanocomposites demonstrated deep pulmonary deposition, confirmed by small MMAD (2.112 µm) and high FPF (77.86%). In vivo investigations in lung cancer animal models revealed the superior anti-tumor efficacy of the inhalable nanocomposites. Overall, the inhalable APBA-HSA nanocomposites offered an alternative strategy for systemic delivery of ETP and BER in lung cancer therapy.

Comparison of Nutrition-Related Adverse Events and Clinical Outcomes Between ICE (Ifosfamide, Carboplatin, and Etoposide) and MCEC (Ranimustine, Carboplatin, Etoposide, and Cyclophosphamide) Therapies as Pretreatment for Autologous Peripheral Blood Stem Cell Transplantation in Patients with Malignant Lymphoma.

BACKGROUND The aim of this study was to compare nutrition-related adverse events and clinical outcomes of ifosfamide, carboplatin, and etoposide regimen (ICE therapy) and ranimustine, carboplatin, etoposide, and cyclophosphamide regimen (MCEC therapy) instituted as pretreatment for autologous peripheral blood stem cell transplantation. MATERIAL AND METHODS We enrolled patients who underwent autologous peripheral blood stem cell transplantation between 2007 and 2012. Outcomes were compared between ICE therapy (n=14) and MCEC therapy (n=14) in relation to nutrient balance, engraftment day, and length of hospital stay. In both groups, we compared the timing of nutrition-related adverse events with oral caloric intake, analyzed the correlation between length of hospital stay and duration of parenteral nutrition, and investigated the association between oral caloric intake and the proportion of parenteral nutrition energy in total calorie supply. Five-year survival was compared between the groups. RESULTS Compared with the MCEC group, the ICE group showed significant improvement in oral caloric intake, length of hospital stay, and timing of nutrition-related adverse events and oral calorie intake, but a delay in engraftment. Both groups showed a correlation between duration of parenteral nutrition and length of hospital stay (P=0.0001) and between oral caloric intake (P=0.0017) and parenteral nutrition energy sufficiency rate (r=-0.73, P=0.003; r=-0.76, P=0.002). Five-year survival was not significantly different between the groups (P=0.1355). CONCLUSIONS Our findings suggest that compared with MCEC therapy, ICE therapy improves nutrition-related adverse events and reduces hospital stay, conserving medical resources, with no significant improvement in long-term survival. The nutritional pathway may serve as a tool for objective evaluation of pretreatment for autologous peripheral blood stem cell transplantation.

A case of molecularly profiled extraneural medulloblastoma metastases in a child.

BACKGROUND: Extraneural metastases are relatively rare manifestations of medulloblastoma. CASE PRESENTATION: We present the case of a young boy with group three MYCN-amplified medulloblastoma. He received multimodal chemotherapy consisting of gross total resection followed by postoperative craniospinal radiation and adjuvant chemotherapy. The patient developed extraneural metastases 4 months after the end of therapy. Literature review identifies the poor prognosis of MYCN-amplified medulloblastomas as well as extraneural metastases; we review the current limitations and future directions of medulloblastoma treatment options. CONCLUSION: To the best of our knowledge, this is the first molecularly characterized report of extraneural metastases of medulloblastoma in a child.

Hemophagocytic Syndrome Complicated with Dermatomyositis Controlled Successfully with Infliximab and Conventional Therapies.

A 57-year-old woman was admitted to our hospital because of a high fever, anemia, and hyperferritinemia. Since a bone marrow examination revealed hemophagocytosis, she was diagnosed with hemophagocytic syndrome (HPS). During treatment of HPS, a heliotrope rash and Gottron's sign appeared with elevated levels of serum aldolase. She also developed heart failure. She was diagnosed with dermatomyositis (DM) and associated myocarditis. Although the administration of glucocorticoids, calcineurin inhibitors, intravenous immunoglobulins, and etoposide ameliorated the clinical findings of DM and cytopenia, the fever and hyperferritinemia remained. The addition of infliximab to glucocorticoids and tacrolimus improved the fever and hyperferritinemia and enabled a reduction in the dose of prednisolone without relapse of the diseases.

Incorporation of high-dose 131I-metaiodobenzylguanidine treatment into tandem high-dose chemotherapy and autologous stem cell transplantation for high-risk neuroblastoma: results of the SMC NB-2009 study.

BACKGROUND: In our previous SMC NB-2004 study of patients with high-risk neuroblastomas, which incorporated total-body irradiation (TBI) with second high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT), the survival rate was encouraging; however, short- and long-term toxicities were significant. In the present SMC NB-2009 study, only TBI was replaced with 131I-meta-iodobenzylguanidine (MIBG) treatment in order to reduce toxicities. METHODS: From January 2009 to December 2013, 54 consecutive patients were assigned to receive tandem HDCT/auto-SCT after nine cycles of induction chemotherapy. The CEC (carboplatin + etoposide + cyclophosphamide) regimen and the TM (thiotepa + melphalan) regimen with (for metastatic MIBG avid tumors) or without (for localized or MIBG non-avid tumors) 131I-MIBG treatment (18 or 12 mCi/kg) were used for tandem HDCT/auto-SCT. Local radiotherapy, differentiation therapy with 13-cis-retinoic acid, and immunotherapy with interleukin-2 were administered after tandem HDCT/auto-SCT. RESULTS: Fifty-two patients underwent the first HDCT/auto-SCT and 47 patients completed tandem HDCT/auto-SCT. There was no significant immediate toxicity during the 131I-MIBG infusion. Acute toxicities during the tandem HDCT/auto-SCT were less severe in the NB-2009 study than in the NB-2004 study. Late effects such as growth hormone deficiency, cataracts, and glomerulopathy evaluated at 3 years after the second HDCT/auto-SCT were also less significant in the NB-2009 study than in NB-2004 study. There was no difference in the 5-year event-free survival (EFS) between the two studies (67.5 ± 6.7% versus 58.3 ± 6.9%, P = 0.340). CONCLUSIONS: Incorporation of high-dose 131I-MIBG treatment into tandem HDCT/auto-SCT could reduce short- and long-term toxicities associated with TBI, without jeopardizing the survival rate. TRIAL REGISTRATION: ClinicalTrials.gov NCT03061656.

Response to anti-programmed cell death protein-1 antibodies in men treated for platinum refractory germ cell cancer relapsed after high-dose chemotherapy and stem cell transplantation.

INTRODUCTION: Treatment options for patients with platinum refractory metastatic germ cell tumours (GCT) relapsing after high-dose chemotherapy and autologous stem cell transplantation are limited and survival is poor. Antibodies directed against programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) are currently assessed within clinical trials. We present updated data on our experience with checkpoint inhibitors as a compassionate use off-label treatment attempt for highly-pretreated patients with GCT and provide an overview of the current literature on PD-L1 expression in this rare tumour entity. PATIENTS AND METHODS: We analysed all patients with platinum refractory GCT treated with checkpoint inhibitors at our institutions between 2015 and 2017. Data were retrieved retrospectively from the patient charts. RESULTS: Seven patients were treated with nivolumab or pembrolizumab. Four patients received single-dose treatment and died shortly afterwards due to tumour progression; the remaining three patients received treatment for at least 6 months. No significant treatment toxicity was observed. Long-term tumour response was achieved in two of the three patients, both of them highly positive for PD-L1 staining. INTERPRETATION: We consider checkpoint inhibition to be efficient in carefully selected patients with platinum refractory GCT. However, predictive markers associated with tumour response are not yet known and larger prospective clinical trials are warranted.

Oral Nanomedicine Based on Multicomponent Microemulsions for Drug-Resistant Breast Cancer Treatment.

The aim of this study is to demonstrate the enhanced therapeutic efficacy of anticancer drugs on drug-resistant breast cancer using multicomponent microemulsions (ECG-MEs) as an oral delivery system. The etoposide-loaded ECG-MEs were composed of coix seed oil and ginsenoside Rh2 (G-Rh2), both of which possess not only the synergistic antitumor effect with etoposide, but also have excipient-like properties. Orally administrated ECG-MEs were demonstrated to be able to accumulate at the tumor site following crossing the intestines as intact vehicles into the blood circulation. The spatiotemporal controlled release characteristics of ECG-MEs brought about the efficient P-gp inhibition by the initially released G-Rh2 and the increased intracellular accumulation of the sequentially released etoposide. The combination antitumor activity of etoposide, G-Rh2 and coix seed oil using ECG-MEs was verified on the xenograft drug-resistant breast tumor mouse models. In addition, the safety evaluation studies indicated that treatment with ECG-MEs did not cause any significant toxicity in vivo. These findings suggest that ECG-MEs as an oral formulation may offer a promising strategy to treat the drug-resistant breast cancer.

Cryptococcus laurentii diarrhea post hematopoietic stem cell transplant.

We report the recent isolation of Cryptococcus laurentii from the feces of a patient with Hodgkin's lymphoma who underwent autologous hematopoietic stem cell transplant (HSCT). The organism was identified using microscopic morphology, cultural characteristics, and biochemical tests including sugar assimilation. Minimum inhibitory concentration of various antifungals was determined by microbroth dilution method. The recovery of pure culture of C. laurentii from stool culture, and the patient's response to treatment with voriconazole support its potential etiological role. To the best of our knowledge, we report the first case of diarrhea caused by C. laurentii in an HSCT recipient.

Antitumor effect of Deoxypodophyllotoxin on human breast cancer xenograft transplanted in BALB/c nude mice model.

Recently, biologically active compounds isolated from plants used in herbal medicine have been the center of interest. Deoxypodophyllotoxin (DPT), structurally closely related to the lignan podophyllotoxin, was found to be a potent antitumor and antiproliferative agent, in several tumor cells, in vitro. However, DPT has not been used clinically yet because of the lack of in vivo studies. This study is the first report demonstrating the antitumor effect of DPT on MDA-MB-231 human breast cancer xenografts in nude mice. DPT, significantly, inhibited the growth of MDA-MB-231 xenograft in BALB/c nude mice. The T/C value (the value of the relative tumor volume of treatment group compared to the control group) of groups treated with 5, 10, and 20 mg/kg of intravenous DPT-HP-ß-CD was 42.87%, 34.04% and 9.63%, respectively, suggesting the positive antitumor activity of DPT. In addition, the antitumor effect of DPT-HP-ß-CD (20 mg/kg) in human breast cancer MDA-MB-231 xenograft was more effective than etoposide (VP-16) (20 mg/kg) and docetaxel (20 mg/kg). These findings suggest that this drug is a promising chemotherapy candidate against human breast carcinoma.