Seminars in oncology最新文献

Immune check point inhibitors (ICI) have secured regulatory approvals across the world for the treatment of various types of cancers. Though not as frequent as immune-related adverse events (AEs) involving other organs, a considerable number of ICI-related renal AE have also been reported and predicting such events has become important. We provide an updated review on possible mechanisms of ICI-related acute kidney injury (AKI), related risk factors, and the use of ICIs in patients with chronic kidney diseases (CKD). A systematic search for related articles was conducted. Acute tubulointerstitial nephritis (ATIN) is known to be the main cause of ICI-related AKI, with glomerulonephritis also a significant cause. Factors including use of concurrent medications, extra-renal immune related AEs, and combination of two or more immunotherapy drugs are possible risk factors. Use of ICI in patients with CKD may be related to increased occurrence of overall immune related AEs. If the diagnosis of ICI related renal AEs is confirmed, prompt use of steroids is recommended, and in severe cases of AKI, discontinuation of ICI should be considered.

Purpose/Objectives

Radiation recall dermatitis (RRD) is a skin reaction limited to an area of prior radiation triggered by the subsequent introduction of systemic therapy. To characterize RRD, we conducted a literature search, summarized RRD features, and compared the most common drug classes implicated in this phenomenon.

Materials/Methods

PubMed, Embase, Scopus, Web of Science, and Cochrane DBSR databases were queried through July 1, 2019 using key words: radiation recall, RRD, and radiodermatitis (limited to humans and English language). Studies included case reports in which patients treated with radiotherapy were initiated on a new line of systemic therapy and subsequently developed a skin reaction in the irradiated area. RRD cases were organized by whether RRD occurred after a single drug or multiple drug administration.

Results

One-hundred fifteen studies representing 129 RRD cases (96 single-drug RRD, 33 multi-drug) were included. Sixty-three drugs were associated with RRD. Docetaxel (22) and gemcitabine (18) were the two drugs most commonly associated with RRD. Breast cancer (69 cases) was the most commonly associated tumor type. For single-drug RRD, the median radiotherapy dose was 45.0 Gy (range, 30.0–63.2 Gy). The median time from radiotherapy to drug exposure, time from drug exposure to RRD and time to significant improvement was 8 weeks (range, 2–132 weeks), 5 days (range, 2–56 days), and 14 days (range, 7–49 days), respectively. Variables significantly associated with grade ≥2 toxicity were docetaxel (P = 0.04) and non-antifolate antimetabolite (P = 0.05). The only variable significantly associated with grade ≥3 toxicity was capecitabine (P = 0.04).

Conclusions

RRD is a complex toxicity that can occur after a wide range of radiotherapy doses and many different systemic agents. Most commonly, it presents in patients diagnosed with breast cancer and after administration of a taxane or antimetabolite medication. RRD treatment generally consists of corticosteroids with consideration of antibiotics if superinfection is suspected. Drug re-challenge may be considered after RRD if the initial reaction was of mild intensity.

Introduction

Patients with cancer need to receive their proper treatment and often cannot wait for their treatment, despite delays due to the COVID-19 pandemic. As a result, many cancer centers have had challenges maintaining their oncological activities.

Objectives

To compare the average hospital management data and indicators in two different periods, with and without the peak of COVID-19 cases, from an important tertiary cancer center in the northeast region of Brazil.

Methods

A retrospective and observational study was performed comparing average hospital administrative data and indicators, between January to March v April to June, 2020 exclusively at the Hospital de Câncer de Pernambuco, Brazil.

Results

There were on average a 13% reduction in the chemotherapy administered (P = .131), 17% fewer radiotherapy treatments carried out (P = .043) and 41% as many oncologic surgeries undertaken (P = .002). There was a reduction in the number of sessions of out-patient chemotherapy of 8•6% (P = .271) and chemotherapy inpatients of 33% (P = .038). Admission of new cases of patients with cancer was reduced by 44% (P = .007) during the period analyzed. Ambulatory appointments also decreased by 55% (P = .004) and emergency room appointments fell by 7•9% (P = .495). The number of hospitalizations was reduced by 36% (P = .005) and the occupancy rate decreased by 23•6% (P = .003), while the length of individual hospital stays (in days) increased 10•5% (P = .116).

Conclusion

We report a reduction in the number of radiotherapy treatments and surgeries performed cancer carried out, ambulatory and emergency appointments, hospitalization and admission of new cases of cancer during peak of COVID-19 in an important public tertiary cancer center in the northeast region of Brazil.

Background

Fluoropyrimidine chemotherapy is used across many tumor types and settings. The incidence of severe adverse events (SAEs) is around 20%. Mortality is 0.5%-1%. Dihydropyrimidine dehydrogenase (DPD) plays a key role in fluoropyrimidine inactivation. Key DPYD mutations are linked to a high risk of SAEs. Pretreatment DPD screening was mandated by EMA guidelines in April 2020 and widely adopted thereafter. Uncertainty remains regarding optimal dosing practice.

Methods

We retrospectively examined records of all 23 patients with DPYD mutation who started chemotherapy between April and November 2020. Our center tests for the mutations considered clinically actionable by Clinical Pharmacogenetics Implementation Consortium and uses the Gene Activity Score (GAS) to guide dose reduction.

Results

Most patients started on a 50% dose. One started on 100% and experienced mild diarrhea after cycle 2; DPD was tested belatedly, subsequent cycles were reduced to 50% and he remained well. Three patients receiving chemo-radiotherapy started on 76% dose; 50% was felt to be subtherapeutic. One of them had no toxicities; another had grade 2 nausea and a hospital attendance with non-neutropenic fever; the third was admitted for 6 weeks with pancolitis. Seven patients did not have toxicities above grade 1 and no hospital attendances. Five patients had further dose reductions. None had dose escalation.

Conclusion

As our experience shows, patients with DPD deficiency are heterogeneous. Worryingly, SAEs occur despite dose reduction according to GAS. Others had minimal toxicity and may be under-dosed by GAS. There are clearly many factors at play other than the 4 DPYD variants. The DPD result must be available and inform first cycle dosing. Dose should be cautiously titrated up if tolerated; this was not done at our center due to clinician caution. Further research is needed to guide this. Patients should be reviewed frequently, counselled regarding their DPD status, and empowered to seek advice promptly when they feel unwell.

Background

Data in patients with malignant melanoma, who have been previously treated with pembrolizumab as adjuvant therapy, show a reduction in pembrolizumab efficacy upon rechallenge. We examined this scenario in patients with non-metastatic renal cell carcinoma (RCC) eligible for adjuvant pembrolizumab after nephrectomy. We hypothesized that a proportion of such patients will either require re-treatment with pembrolizumab upon metastatic progression prior to cancer-specific mortality (CSM) or die from other cause mortality (OCM).

Materials and methods

We identified within the SEER database 10,635 patients, between 2004 and 2017, with a diagnosis of non-metastatic intermediate-high and high risk RCC, who had undergone nephrectomy and fulfilled criteria for enrollment in KEYNOTE-564. Kaplan-Meier analyses addressed overall survival (OS), CSM and OCM.

Results

9,825 (92.4%) of the 10,635 patients had intermediate-high risk RCC and 9,456 (88.9%) underwent radical nephrectomy. Additionally, 760 (7.1%) harbored sarcomatoid features. In Kaplan-Meier analyses, median OS was 9.8 (9.1–11.4) years. At 10-years of follow-up, CSM rate was 36% and OCM rate was 22%.

Conclusions

Based on CSM, our observations indicate that by 10-years of follow-up 36% of patients treated with adjuvant pembrolizumab will require a rechallenge, in a setting where a checkpoint inhibitor may have reduced efficacy. Moreover, at 10-years of follow-up, 22% of patients with RCC, previously treated with adjuvant pembrolizumab, will die of other causes. These percentages should be strongly considered prior to routine use of adjuvant pembrolizumab, especially given an OS benefit has not been proven.

Imaging innovations offer useful techniques applicable to many oncology specialties. Treatment advances in the field of multiple myeloma (MM) have increased the need for accurate diagnosis, particularly in the bone marrow, which is an essential component in myeloma-defining criteria. Modern imaging identifies osteolytic lesions, distinguishes solitary plasmacytoma from MM, and evaluates the presence of extramedullary disease. Furthermore, imaging is increasingly valuable in post-treatment response assessment. Detection of minimal residual disease after therapy carries prognostic implications and influences subsequent treatment planning.

Whole-body low-dose Computed Tomography is now recommended over the conventional skeletal survey, and more sophisticated functional imaging methods, such as ¹⁸F-Fluorodeoxyglucose Positron Emission Tomography , and diffusion-weighted Magnetic Resonance Imaging are proving effective in the assessment and monitoring of MM disease. This review focuses on understanding indications and advantages of these imaging modalities for diagnosing and managing myeloma.

Multiple myeloma is a common hematological malignancy of plasma cells, the terminally differentiated B cells that secrete antibodies as part of the adaptive immune response. Significant progress has been made in treating multiple myeloma, but this disease remains largely incurable, and most patients will eventually suffer a relapse of disease that becomes refractory to further therapies. Moreover, a portion of patients with multiple myeloma present with disease that is refractory to all treatments from the initial diagnosis, and no current therapeutic approaches can help. Therefore, the task remains to advance new therapeutic strategies to help these vulnerable patients. One strategy to meet this challenge is to unravel the complex web of pathogenic signaling pathways in malignant plasma cells and use this information to design novel precision medicine strategies to assist these patients most at risk.

As is the case for solid tumors, treatment paradigms have shifted from non-specific chemotherapeutic agents towards novel targeted drugs in the treatment of patients with multiple myeloma (MM). Currently, multiple targeted therapies are available to treat patients augmenting the arsenal of modalities which also includes chemotherapy, immunotherapy, radiation therapy, hematopoietic stem cell transplantation (HSCST) and chimeric antigen T-cell therapy (CAR-T). These novel, targeted agents have dramatically increased optimism for patients, who may now be treated over many years with successive regimens. As fortunate as we are to have these new therapies available for our patients, this advantage is juxtaposed with the challenges involved with delivering them safely. While each class of agents has demonstrated efficacy, in terms of response rates and survival, they also exert class effects which pose risks for toxicity. In addition, newer generation agents within the classes often have slightly different toxicity profiles than did their predecessors. These factors must be addressed, and their risks mitigated by the multidisciplinary team. This review presents a summary of the evolution of drug development for MM. For each targeted agent, the efficacy data from pivotal trials and highlights of the risks that were demonstrated in trials, as well as during post-marketing surveillance, are presented. Specific risks associated with agents within the classes, that are not shared with all new class members, are described. A table presenting these potential risks, with recommended nursing actions to mitigate toxicity, is provided as a quick reference that nurses may use during the planning, and provision, of patient care.