Preceding standard therapy is the likely cause of MDS after autotransplants for multiple myeloma

Myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) have been reported after autologous transplantation (AT) for lymphoma. It is not clear whether myeloablative therapy used in conjunction with autologous transplantation contributes to the development of MDS/AML or whether the conventional chemotherapy preceding the transplant, and administered over a prolonged period, causes these secondary malignancies. To address this issue, we examined 188 patients with multiple myeloma (MM) who had received AT. 71 patients with no more than one cycle of standard chemotherapy were enrolled in our Total Therapy program, designed to avoid exposure to alkylating agents prior to peripheral blood stem cell mobilization (group 1). The median duration of pre-transplant therapy in group 1 was 7.6 months and significantly shorter than the 24 months of 117 patients (group 2) with more prolonged conventional therapy ( P  = 0.0001). All seven patients developing MDS post-transplantation belonged to group 2 ( P  = 0.02); the median durations from initial therapy and first transplant were 66 months (range 38–86) and 24 months (range 9–39), respectively. Our findings provide evidence that prolonged standard-dose alkylating agent therapy prior to transplantation, rather than autotransplant-supported myeloablative treatment, is associated with development of MDS/AML. Stem cell damaging alkylator treatment should be avoided, not to compromise PBSC collection, but also to reduce the risk of treatment-related MDS/AML.     

Validation of a simple resazurin-based promastigote assay for the routine monitoring of miltefosine susceptibility in clinical isolates of Leishmania donovani

Simple, cost-effective approach for routine surveillance of parasite susceptibility to antileishmanial drug miltefosine (MIL) is highly desirable for controlling emergence of drug resistance in visceral leishmaniasis (VL). We validated a simple resazurin-based fluorimetric assay using promastigotes to track natural MIL tolerance in Leishmania donovani parasites from VL cases (n?=?17) against standard amastigote assay, in two different labs in India. The inter-stage MIL susceptibility correlated strongly (r?=?0.70, p?=?0.0018) using J774.A.1 macrophage cell line-based amastigote assay and fluorescence-based resazurin assay for promastigotes. Investigation of inter-stage MIL susceptibility for the same set of clinical isolates in another lab also showed a strong correlation (r?=?0.72, p?=?0.0012) using mouse peritoneal macrophages for amastigote assay and resazurin-based alamar blue assay for promastigotes. Additionally, parasites from post-kala-azar dermal leishmaniasis (PKDL) lesions (n?=?7, r?=?0.78, p?=?0.046) and MIL-induced parasites (r?=?0.92, p?=?0.0001; n?=?3) also exhibited a strongly correlated inter-stage miltefosine susceptibility. Thus, our results support the utility of resazurin assay as a simplified biological tool for MIL susceptibility monitoring in clinical isolates from MIL-treated VL/PKDL patients.     

Resolution of Persistent COVID-19 After Convalescent Plasma in a Patient with B Cell Aplasia

Journal of Clinical Immunology -     

Artificial intelligence in brachytherapy: a summary of recent developments

Artificial intelligence (AI) applications, in the form of machine learning and deep learning, are being incorporated into practice in various aspects of medicine, including radiation oncology. Ample evidence from recent publications explores its utility and future use in external beam radiotherapy. However, the discussion on its role in brachytherapy is sparse. This article summarizes available current literature and discusses potential uses of AI in brachytherapy, including future directions. AI has been applied for brachytherapy procedures during almost all steps, starting from decision-making till treatment completion. AI use has led to improvement in efficiency and accuracy by reducing the human errors and saving time in certain aspects. Apart from direct use in brachytherapy, AI also contributes to contemporary advancements in radiology and associated sciences that can affect brachytherapy decisions and treatment. There is a renewal of interest in brachytherapy as a technique in recent years, contributed largely by the understanding that contemporary advances such as intensity modulated radiotherapy and stereotactic external beam radiotherapy cannot match the geometric gains and conformality of brachytherapy, and the integrated efforts of international brachytherapy societies to promote brachytherapy training and awareness. Use of AI technologies may consolidate it further by reducing human effort and time. Prospective validation over larger studies and incorporation of AI technologies for a larger patient population would help improve the efficiency and acceptance of brachytherapy. The enthusiasm favoring AI needs to be balanced against the short duration and quantum of experience with AI in limited patient subsets, need for constant learning and re-learning to train the AI algorithms, and the inevitability of humans having to take responsibility for the correctness and safety of treatments.     

Internal target volume for post-hysterectomy vaginal recurrences of cervical cancers during image-guided radiotherapy

Objective:

The outcome of post-surgical recurrences of cervical cancer may be improved through radiation dose escalation, which hinges on accurate identification and treatment of the target. The present study quantifies target motion during course of image-guided radiotherapy (IGRT) for vault cancers.

Methods:

All patients underwent planning CT simulation after bladder-filling protocol. A daily pre-treatment megavoltage CT was performed. All translations and rotations were recorded. Post-registration displacement of gross tumour volume (GTV) and centre of mass (COM) of GTV was independently recorded by two observers for fractions one to seven. Day 1 image sets served as reference images against which the displacements of COM were measured. We calculated the displacements of common volume (CV) and encompassing volume (EV) of GTV for both the observers.

Results:

A total of 90 image data sets of 15 patients were available for evaluation. Individual patient GTV and average GTV by both the observers were comparable. The average shifts for EV were 2.4 mm [standard deviation (SD) ±1.2] in the mediolateral, 4.2 mm (SD ±2.8) in the anteroposterior and 4.0 mm (SD ±2.1) in superoinferior directions. Similarly, the average shifts for CV were 1.9 mm (SD ±0.6) in the mediolateral, 3.7 mm (SD ±2.7) in the anteroposterior and 4.4 mm (SD ±2.7) in superoinferior directions. Using Stroom''s/van Herk''s formula, the minimum recommended margins would be 4.5/5.2, 8.2/9.4 and 7.3/8.3 mm, respectively, for lateral, anteroposterior and superoinferior directions.

Conclusion:

Differential directional internal margin is recommended in patients undergoing IGRT for post-surgical recurrence of cervical cancers.

Advances in knowledge:

Internal organ motion of vault cancers can be accounted for by a directional margin to the gross tumour.     

Repeatability of hypoxia PET imaging using [<Superscript>18</Superscript>F]HX4 in lung and head and neck cancer patients: a prospective multicenter trial

Purpose

Hypoxia is an important factor influencing tumor progression and treatment efficacy. The aim of this study was to investigate the repeatability of hypoxia PET imaging with [¹⁸F]HX4 in patients with head and neck and lung cancer.

Methods

Nine patients with lung cancer and ten with head and neck cancer were included in the analysis (NCT01075399). Two sequential pretreatment [¹⁸F]HX4 PET/CT scans were acquired within 1 week. The maximal and mean standardized uptake values (SUV_max and SUV_mean) were defined and the tumor-to-background ratios (TBR) were calculated. In addition, hypoxic volumes were determined as the volume of the tumor with a TBR >1.2 (HV_1.2). Bland Altman analysis of the uptake parameters was performed and coefficients of repeatability were calculated. To evaluate the spatial repeatability of the uptake, the PET/CT images were registered and a voxel-wise comparison of the uptake was performed, providing a correlation coefficient.

Results

All parameters of [¹⁸F]HX4 uptake were significantly correlated between scans: SUV_max (r?=?0.958, p?<?0.001), SUV_mean (r?=?0.946, p?<?0.001), TBR_max (r?=?0.962, p?<?0.001) and HV_1.2 (r?=?0.995, p?<?0.001). The relative coefficients of repeatability were 15 % (SUV_mean), 17 % (SUV_max) and 17 % (TBR_max). Voxel-wise analysis of the spatial uptake pattern within the tumors provided an average correlation of 0.65?±?0.14.

Conclusion

Repeated hypoxia PET scans with [¹⁸F]HX4 provide reproducible and spatially stable results in patients with head and neck cancer and patients with lung cancer. [¹⁸F]HX4 PET imaging can be used to assess the hypoxic status of tumors and has the potential to aid hypoxia-targeted treatments.

     

Clinical factors predictive of outcome with bortezomib in patients with relapsed, refractory multiple myeloma

Bortezomib, a potent and reversible proteasome inhibitor, affects the myeloma cell and its microenvironment, resulting in down-regulation of growth and survival signaling pathways and durable responses in patients with relapsed and refractory myeloma. Potential associations between baseline parameters and outcomes with bortezomib were explored in 202 patients who received bortezomib 1.3 mg/m2 twice weekly for 2 weeks every 3 weeks for up to 8 cycles in a phase 2 trial. Using European Group for Blood and Marrow Transplantation criteria, the response rate (complete or partial response) to bortezomib alone was 27% and was not associated with sex, race, performance status, isotype, chromosome 13 deletion, number or type of previous therapies, or concentration of hemoglobin or beta2-microglobulin. By multivariate analysis, factors associated with lower response were being age 65 or older versus younger than 65 (19% vs 32%; P < .05) and plasma-cell infiltration in bone marrow greater than 50% versus 50% or less (20% vs 35%; P < .05). Factors that may be indicative of tumor burden (bone marrow plasma-cell infiltration greater than 50%, hypoalbuminemia, thrombocytopenia) were predictive of overall survival. Chromosome 13 deletion and elevated beta2-microglobulin, generally considered poor prognostic factors, were not predictive of poor outcome with bortezomib in this study.     

Molecular Evidence of Helicobacter Pylori Infection in Prostate Tumors

Objectives

To determine whether Helicobacter pylori (H. pylori) is detectable in both benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Epidemiological studies have shown significant associations between infective chronic prostatitis and prostatic carcinoma. Many bacteria have been found in the prostate of patients with chronic prostatitis, BPH, and PCa.

Methods

One hundred consecutive patients with prostate diseases were enrolled in the study. Detection of H. pylori DNA in prostate tissue from patients with BPH and PCa was performed using both immunohistochemistry and PCR, and the results were confirmed by DNA sequencing. Odds ratios and the Fisher Exact test were used for the analysis of the associations between the variables.

Results

Among the patients, 78% had BPH and 19% had PCa. While immunohistochemistry showed no positive sample for H. pylori, PCR combined with sequencing detected H. pylori DNA in prostate tissue samples from 5 patients. However, statistical analysis of the data showed that BPH and PCa are not significantly associated with the presence of H. pylori DNA in prostate tissue (odds ratio = 0.94, 95% confidence interval = 0.09–23.34, one-tailed Chi-square value = 0.660, p > 0.05). The limitation of this study was the small number of PCa patients.

Conclusions

This study provides, for the first time, molecular evidence of the presence of H. pylori DNA in prostatic tissue of patients with BPH and PCa. It paves the way for further comprehensive studies to examine the association of H. pylori infection with BPH and PCa.Key Words: Helicobacter pylori infection, Prostate cancer, Benign prostate hyperplasia, PCR