Palmar-plantar erythrodysesthesia secondary to docetaxel chemotherapy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Docetaxel is a chemotherapeutic agent used alone or in combination for the management of many neoplastic conditions. Numerous side effects are well described as a consequence. Palmar-plantar erythrodysesthesia, although a relatively common side effect of some types of chemotherapy, occurs infrequently with docetaxel and is often attributed to other drug agents.</p> <p>Case Presentation</p> <p>We report the case of a 66-year-old Caucasian woman who received adjuvant docetaxel monotherapy for invasive breast cancer. She developed palmar-plantar erythrodysesthesia following her first cycle of treatment, which necessitated a change in management.</p> <p>Conclusion</p> <p>Palmar-plantar erythrodysesthesia is a relatively common side effect of cytotoxic chemotherapy, particularly with drugs such as 5-fluorouracil, capecitabine and liposomal doxorubicin. Docetaxel is commonly used both alone and in combination with a number of these agents for the management of various malignant conditions. We would like to highlight the occurrence of palmar-plantar erythrodysesthesia as a result of docetaxel monotherapy so that it can be considered as a potential cause in patients receiving combination treatment with chemotherapeutic agents better known to cause this toxicity.</p

Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response.

BACKGROUND: Sunitinib prolongs progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumours (pNET). Response Evaluation Criteria in Solid Tumors (RECIST)-defined partial responses (PR; classically defined as ⩾30% size decrease from baseline) are infrequent. METHODS: Individual data of pNET patients from the phase II [NCT00056693] and pivotal phase III [NCT00428597] trials of sunitinib were analysed in this investigator-initiated, post hoc study. The primary objective was to determine the optimal RECIST (v.1.0) response cut-off value to identify patients who were progression-free at 11 months (median PFS in phase III trial); and the most informative time-point (highest area under the curve (AUC) by receiver operating characteristic (ROC) analysis and logistic regression) for prediction of benefit (PFS) from sunitinib. RESULTS: Data for 237 patients (85 placebo; 152 sunitinib (n=66.50 mg \u274-weeks on/2-weeks off\u27 schedule; n=86 \u2737.5 mg continuous daily dosing (CDD)\u27)) and 788 scans were analysed. The median PFS for sunitinib and placebo were 9.3 months (95% CI 7.6-12.2) and 5.4 months (95% CI 3.5-6.01), respectively (hazard ratio (HR) 0.43 (95% CI 0.29-0.62); P CONCLUSIONS: A 10% reduction within marker lesions identifies pNET patients benefiting from sunitinib treatment with implications for maintenance of dose intensity and future trial design

The influence of soil communities on the temperature sensitivity of soil respiration

Soil respiration represents a major carbon flux between terrestrial ecosystems and the atmosphere, and is expected to accelerate under climate warming. Despite its importance in climate change forecasts, however, our understanding of the effects of temperature on soil respiration (RS) is incomplete. Using a metabolic ecology approach we link soil biota metabolism, community composition and heterotrophic activity, to predict RS rates across five biomes. We find that accounting for the ecological mechanisms underpinning decomposition processes predicts climatological RS variations observed in an independent dataset (n = 312). The importance of community composition is evident because without it RS is substantially underestimated. With increasing temperature, we predict a latitudinal increase in RS temperature sensitivity, with Q10 values ranging between 2.33 ±0.01 in tropical forests to 2.72 ±0.03 in tundra. This global trend has been widely observed, but has not previously been linked to soil communities

Early MRI response monitoring of patients with advanced hepatocellular carcinoma under treatment with the multikinase inhibitor sorafenib

<p>Abstract</p> <p>Background</p> <p>New therapeutic principles in clinical oncology require the adjustment of response criteria to govern therapy decisions. For advanced hepatocellular carcinoma (HCC) a new era has recently begun by the approval of the multikinase inhibitor sorafenib. As a unique feature, HCC usually develops in a diseased liver and current imaging technologies employing classical response criteria have not been prospectively evaluated for this new treatment.</p> <p>Methods</p> <p>MRI signal patterns were assessed in 21 advanced HCC patients receiving sorafenib. MRI was performed at baseline and in short-term intervals thereafter. Signal changes under therapy on T1WI, T2WI and post-gadolinium images including necrosis volume and its ratio to the entire tumor volume were compared to baseline imaging. To assess the association between the categorical variables, Fisher's exact tests were applied for a statistical analysis. Survey time ranged from 2–65 weeks, and a total of 39 target lesions were evaluated.</p> <p>Results</p> <p>Signal abnormalities during sorafenib therapy were disclosed by T1WI and T2WI in 15/21 patients. The predominant tumor signal change was hyperintensity on both T1WI and T2WI. Interestingly, most patients developed MRI signal changes within 4 weeks of therapy; in contrast, two non-responders did not show any signal alteration at follow-up. Under therapy, 16/21 patients presented with new or progressive necrosis, whereas 7 patients achieved temporarily >75% tumor necrosis under sorafenib. Significantly associated MRI variables were increase in T1WI signal and tumor necrosis (p = 0.017) as well as increase of tumor necrosis with an elevated ratio of necrotic to vital tumor areas (p = 0.002). Remarkably, some (3/13) of the patients developing necrotic tumor areas showed a relevant (>20%) increase in tumor volume, which should be considered in the assessment of imaging studies.</p> <p>Conclusion</p> <p>As sorafenib induces early intralesional necrosis with profound changes in T1WI/T2WI MRI signal intensities and measurable necrotic tumor areas in most HCC patients, early MRI-based evaluation could pave the way for its rationale and cost-effective application.</p

MIA-Prognosis: A Deep Learning Framework to Predict Therapy Response

Predicting clinical outcome is remarkably important but challenging. Research efforts have been paid on seeking significant biomarkers associated with the therapy response or/and patient survival. However, these biomarkers are generally costly and invasive, and possibly dissatifactory for novel therapy. On the other hand, multi-modal, heterogeneous, unaligned temporal data is continuously generated in clinical practice. This paper aims at a unified deep learning approach to predict patient prognosis and therapy response, with easily accessible data, e.g., radiographics, laboratory and clinical information. Prior arts focus on modeling single data modality, or ignore the temporal changes. Importantly, the clinical time series is asynchronous in practice, i.e., recorded with irregular intervals. In this study, we formalize the prognosis modeling as a multi-modal asynchronous time series classification task, and propose a MIA-Prognosis framework with Measurement, Intervention and Assessment (MIA) information to predict therapy response, where a Simple Temporal Attention (SimTA) module is developed to process the asynchronous time series. Experiments on synthetic dataset validate the superiory of SimTA over standard RNN-based approaches. Furthermore, we experiment the proposed method on an in-house, retrospective dataset of real-world non-small cell lung cancer patients under anti-PD-1 immunotherapy. The proposed method achieves promising performance on predicting the immunotherapy response. Notably, our predictive model could further stratify low-risk and high-risk patients in terms of long-term survival.Comment: MICCAI 2020 (Early Accepted; Student Travel Award

Late-onset benefit in progressive advanced hepatocellular carcinoma with continued sorafenib therapy: a case report

<p>Abstract</p> <p>Introduction</p> <p>In the past, no effective systemic therapy has existed for patients with advanced hepatocellular carcinoma. Sorafenib, an oral multikinase inhibitor, has recently been shown to improve overall survival in patients with advanced hepatocellular carcinoma in two randomized, double-blinded, placebo-controlled trials. This drug has been approved as the first-line therapy for advanced hepatocellular carcinoma patients. We report an intriguing case of advanced hepatocellular carcinoma in which the patient achieved late- onset partial response by prolonged administration of sorafenib in spite of progressive disease.</p> <p>Case presentation</p> <p>A 54-year-old Japanese man was treated with sorafenib for multiple lung metastases after surgical resection for advanced hepatocellular carcinoma accompanied by vascular invasion of the left branch of the portal vein. Although the effective diagnosis was progressive disease, almost all sites began to reduce or disappear eight months after the diagnosis of progressive disease. A dramatic reduction in alpha-fetoprotein and des-gamma-carboxy prothrombin levels was observed. The patient finally achieved partial response and his status remains unchanged.</p> <p>Conclusions</p> <p>If tolerated, prolonged sorafenib treatment may be beneficial.</p

Unresectable gastric cancer with gastric outlet obstruction and distant metastasis responding to intraperitoneal and folfox chemotherapy after palliative laparoscopic gastrojejunostomy: report of a case

<p>Abstract</p> <p>Background</p> <p>Gastric outlet obstruction (GOO) caused by unresectable gastric cancer is a challenging aspect of patient care. There have been no reports involving patients with obstructing gastric cancer and several incurable factors curatively treated by multimodal treatments.</p> <p>Case presentation</p> <p>We report a case of 55-year-old man who was diagnosed with a poorly differentiated adenocarcinoma in the pre-pyloric antrum with GOO by gastroscopy. An abdominal computed tomography (CT) scan revealed thickening of the gastric wall and adjacent fat infiltration, and a large amount of food in the stomach suggesting a passage disturbance, enlarged lymph nodes along the common hepatic and left gastric arteries, and multiple hepatic metastases. The serum carcinoembryonic antigen (CEA) level was 343 ng/ml and the carbohydrate antigen (CA) 19-9 level was within normal limits. The patient underwent a laparoscopic gastrojejunostomy for palliation of the GOO. On the 3^rdand 12^thdays after surgery, he received intraperitoneal chemotherapy with 40 mg of docetaxel and 150 mg of carboplatin. Simultaneously, combined chemotherapy with 85 mg/m²of oxaliplatin for the 1^stday and 600 mg/m²of 5-FU for 2 days (FOLFOX regimen) was administered from the 8^thpost-operative day. After completion of nine courses of FOLFOX, the patient achieved a complete response (CR) with complete disappearance of the primary tumor and the metastatic foci. He underwent a radical subtotal gastrectomy with D3 lymph node dissection 4 months after the initial palliative surgery. The pathologic results revealed no residual primary tumor and no lymph node metastasis in 43 dissected lymph nodes. He has maintained a CR for 18 months since the last operation.</p> <p>Conclusion</p> <p>Combination chemotherapy with systemic and intraperitoneal chemotherapy following laparoscopic bypass surgery showed marked efficacy in the treatment for unresectable advanced gastric cancer with GOO.</p

Patient-centric trials for therapeutic development in precision oncology

An enhanced understanding of the molecular pathology of disease gained from genomic studies is facilitating the development of treatments that target discrete molecular subclasses of tumours. Considerable associated challenges include how to advance and implement targeted drug-development strategies. Precision medicine centres on delivering the most appropriate therapy to a patient on the basis of clinical and molecular features of their disease. The development of therapeutic agents that target molecular mechanisms is driving innovation in clinical-trial strategies. Although progress has been made, modifications to existing core paradigms in oncology drug development will be required to realize fully the promise of precision medicine