End-of-life Comfort Evaluation, is Clinic Enough? A Retrospective Cohort Study of Combined Comfort Evaluation with Analgesia/Nociception Index and Clinic in non-Communicative Patients

Background: Comfort evaluation is one of the major challenges in the palliative care setting, particularly when it comes to non-communicative patients. For this specific population, validated tools for comfort evaluation are scarce and healthcare professionals have to rely on their clinical sense and experience. Objectives: To provide arguments for the use of Analgesia/Nociception Index (ANI) monitoring in order to improve clinical comfort evaluation. Methods: We conducted a retrospective cohort study of non-communicative patients at the end of their lives whose comfort was evaluated clinically and with ANI. We focused on the coherence or discordance of clinical and ANI evaluations and on pharmacological interventions driven by them. Results: 58 evaluations from 33 patients were analyzed. Clinical and demographic characteristics were highly variable. Simultaneous clinical and ANI evaluations were concordant in 45 measurements (77.58%), leading mostly to no treatment modification when indicating comfort and to increasing anxiolytic or pain-relief treatments when indicating discomfort. Thirteen (22.41%) evaluations were discordant, leading mostly to treatment incrementation. Conclusion: We suggest that the ANI monitor is a reliable tool in the palliative setting and may help provide patients with the best symptom relief and the most appropriate therapeutics.

A Successful Chemoembolization of a Retroperitoneal Soft Tissue Sarcoma: A Case Report

Retroperitoneal sarcomas are rare entities. They have a tendency of growing slowly, rendering the patient apparently healthy for long periods of time, before diagnosis. Besides, they have a worse prognosis than sarcomas arising in extremities, with a higher local recurrence rate and lower 5-year survival rate. We describe a case of a 71-year-old male patient, who had a very well succeeded treatment of a large retroperitoneal sarcoma with the combination of chemoembolization, systemic chemotherapy, surgery, and radiation therapy. Initially, it was noticed in an incidental way he had a large retroperitoneal mass (15 cm × 10 cm × 9.2 cm) through magnetic resonance, when he was 63. The case was considered inoperable by the treating physicians. After neoadjuvant therapy, the residual tumor could be completely excised by the responsible surgeon. With a follow-up of >5 years, since the end of treatment, the patient remains in complete remission and, probably, cured from his illness. Large retroperitoneal sarcomas are still a great challenge for oncologists. According to the medical literature, chemoembolization can benefit some patients, but most of them in a palliative setting. In our report, we believe its contribution was critical for a great outcome. In selected cases, it is possible this procedure may be an additional therapeutic modality, as part of a multidisciplinary approach.

Cause of Death in Patients in Radiation Oncology

BackgroundThe accurate attribution of death in oncologic patients is a difficult task. The patient’s death is often attributed to his or her underlying cancer and therefore judged as cancer-related. We hypothesized that even though our patient’s cancers were either advanced or metastatic, not all patients had died simply because of their cancer.MethodsA total of 105 patients were included in this retrospective analysis. Patient data were collected from digital and paper-based records. Cause of death was assessed from death certificate and compared to the medical autopsy reports. Discrepancies between premortem and postmortem diagnoses were classified as class I and II discrepancies.ResultsOf 105 patients included, autopsy consent was obtained in 56 cases (53%). Among them, 32 of 56 were palliatively sedated, and 42/56 patients died cancer-related as confirmed by autopsy. The most common cause of death by autopsy report was multiorgan failure followed by a combination of tumor and infection, predominantly lung cancer with pneumonia. Here, 21/56 cases (37%) showed major missed diagnoses: seven cases showed class I, 10 class II, and both discrepancies. The most commonly missed diagnoses in both categories were infections, again mainly pneumonia.ConclusionsCancer was the leading cause of death in our study population. A quarter of the patients, however, did not die due to their advanced or metastatic cancers but of potentially curable causes. We therefore conclude that it is important to consider competing causes of death when treating palliative cancer patients. In a palliative setting, the treatment of a potentially curable complication should be discussed with the patients and their families in a shared decision-making process. From our experience, many patients will decline treatment or even further diagnostics when given the option of best supportive care.

Laparoscopic Heated Intraperitoneal Chemotherapy in the Treatment of Carcinomatosis of Gastric Adenocarcinoma Origin

The use of heated intraperitoneal chemotherapy (HIPEC) in conjunction with cytoreductive surgery has been gaining increasing traction in treating gastric adenocarcinoma with metastasis to the peritoneum in recent years. The addition of laparoscopic HIPEC (LS-HIPEC) to these treatment algorithms has increased the flexibility and adaptability of HIPEC integrating into treatment sequencing, allowing for iterative protocols of LS-HIPEC prior to cytoreduction as neoadjuvant treatment, as well as in the palliation of patients with unresectable disease and uncontrolled ascites. As the use of HIPEC in gastric adenocarcinoma continues to be refined, LS-HIPEC algorithms should continue to be considered and utilized both in curative treatment algorithms as well as in patients in the palliative setting. Given that LS-HIPEC remains a relatively nascent treatment modality, we advocate for its use in the setting of a clinical trial when feasible.

Stoma-related considerations in palliative patients

In the community there are about 200 000 people with a stoma. Some of these may have been performed as a palliative procedure to relieve a bowel obstruction, for example. Alternatively, the condition of the patient may have altered. A person with a stoma may, for many reasons, be approaching the end of life. There are a number of stoma-related issues that can occur at the end of life as a result of cancer treatment, such as skin around the stoma being damaged as a result of chemotherapy or changes in weight. In the palliative setting, patients may no longer be able to independently care for their stoma and may require assistance from the community nurse. Input from the community nurse may include information on changing stool consistency, as a result of disease progression or cancer treatment. Alternatively, nursing input might be necessary to train carers to perform stoma care. Community nurses can also provide knowledge to patients to improve understanding and decrease anxiety at the end of life.

Pressurized Intraperitoneal Aerosol Chemotherapy-Related Clinical Trials in the Treatment of Peritoneal Metastases

<b><i>Introduction:</i></b> Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a treatment option for patients with peritoneal metastases. We evaluated the current status of ongoing prospective clinical trials investigating PIPAC to provide an overview and predict trends in this field. <b><i>Methods:</i></b> All 367,494 records of clinical trials registered at ClinicalTrials.gov were searched for trials dealing with PIPAC. Active or unpublished trials were further analyzed. <b><i>Results:</i></b> In total, 22 clinical trials were identified and selected for further analyses. Most trials had a single-arm design and were phase I or II. No phase III trials were registered. Academic centers were recorded as primary sponsors in the majority of trials (63.6%). Every year, between 2 and 5 new trials were initiated. In 17 trials (81.8%), PIPAC was used in a palliative setting only, 2 trials performed PIPAC in a neoadjuvant setting, and 2 trials performed PIPAC in an adjuvant setting. Six different drugs (doxorubicin, cisplatin, oxaliplatin, nab-paclitaxel, 5-fluorouracil, and docetaxel) were used in these clinical trials. Most trials investigated the efficacy (<i>n</i> = 15) or safety (<i>n</i> = 7) of PIPAC therapies. <b><i>Conclusions:</i></b> The results of ongoing clinical trials will bring specific information on indications for PIPAC as well as the impact of PIPAC on quality of life and overall survival.

New WHO guidelines for cancer pain in adults and adolescents

In this article we performed publication analysis devoted to pain medicine in oncology during anticancer therapy and in palliative setting. Until recently, the main WHO guidelines for pain management in oncology were the recommendations of 1996, which included only pain relievers, as well as adjuvant and symptomatic drugs, which were applied according to the WHO analgesic ladder. These recommendations were based on the collective expert opinion of leading clinicians and scientists. The new WHO clinical guidelines were published in 2019. They are based on the principles of evidence-based medicine, including modern concepts of the etiology and pathogenesis of tumor pain syndrome. This recommendations contain sections on the analgesic efficacy of radiation therapy and antitumor drug therapy. The new WHO recommendations have not yet been published in Russian and are not sufficiently available for a wide range of oncologists and palliative specialists in our country. The purpose of this publication is to present within one volume a concise but complete and comprehensible discussion of the latest trends in pain therapy in oncology, published by WHO experts.

RADIATION IN A PALLIATIVE SETTING DURING COVID-19 ERA. AN INDIAN TERTIARY CANCER CARE PROSPECTIVE – RISKS, BENEFITS .

India and the rest of the world are experiencing an outbreak of the COVID- 19 virus. WHO has declared 2019 novel coronavirus disease (COVID19), a public health emergency of international concern. (1) Palliative treatment compromises a major portion of radiation treatments in cancer. (2) Metastatic or palliation treatment presents a unique challenge in resource-limited settings as ours and early treatment to alleviate their symptoms and disease is the need of the hour to prevent further morbidity and mortality. These patients are usually more cachexic with low immunity and more prone to infection of COVID-19 than the normal population, here their treatment has to be expedited and their visits to the hospital to be minimized to prevent infection with COVID. (3) We reviewed the best evidence and recommended best practices for the treatment of common oncologic emergencies with more emphasis on balancing the risk of infection with the COVID-19 virus and the potential morbidity of delaying treatment. In COVID -19 Era pandemic, the use of hypofractionated radiation therapy for palliative patients for oncologic emergencies achieves intended functional outcomes without compromising care

Overall survival, quality of life and magnitude of clinical benefit of breast cancer drugs over the last 25 years.

6571 Background: The American Society of Clinical Oncology Cancer Research Committee (ASCO-CRC), the ASCO Value Framework Net Health Benefit score version 2 (ASCO-VF), and the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS) are validated tools quantifying the clinical benefit for cancer drugs. Here, we assess the overall survival (OS), quality of life (QoL) and magnitude of clinical benefit of trials supporting breast cancer drug approval by the US Food and Drug Administration (FDA) in the last 25 years. Methods: We searched Drugs@FDA website for all breast cancer drug approvals from January 1, 1995 to December 30, 2020. Drug labels and reports of registration trials were reviewed. We collected data on trial characteristics, efficacy, toxicity and QoL. When more than one study supported a single indication, we preferred efficacy-oriented endpoints (typically OS) to QoL. We excluded trials supporting accelerated-approval indications if these were converted to regular approval during the study period. We scored clinical benefit using the ASCO-CRC in palliative setting, and ASCO-VF and ESMO-MCBS in both curative and palliative setting. Substantial clinical benefit was defined as: OS gains ≥2.5 months and progression-free survival gains ≥ 3 months for ASCO-CRC criteria; ASCO-VF scores ≥ 45 and grade of A or B for trials of curative intent and 4 or 5 for those of non-curative intent using ESMO-MCBS. Trends over time were assessed using Chi-squared test for trend. Results: We identified 51 trials supporting the approval of 32 individual drugs for 51 indications; 12 (24%) were in the curative setting and 39 (76%) in the palliative setting. At the time of approval, 8 (16%) trials reported significant improvement in OS. QoL was reported in 22 trials (43%). Among these, 8 (36%) showed improvement in QoL. For curative intent, we applied ASCO-VF and ESMO-MCBS score to 11 (92%) trials, finding clinical benefit in 10 (91%) and 2 (18%) trials, respectively. In the palliative setting, we used ASCO-CRC, ASCO-VF and ESMO-MCBS scores to rate 32 (82%), 33 (85%) and 38 (97%) trials. Substantial clinical benefit was observed in 20 (63%), 12 (36%) and 7 (19%) trials, respectively. Over time, there has been a decrease in the number of trials supporting approval based on OS (1996-2003 50% vs 2004-12 38% vs 2013-20 13%, P trend = 0.033). There were no statistically significant changes over time in QoL, ASCO-CRC, ASCO-VF and ESMO-MCBS scores. Conclusions: For palliative intent, most trials supporting FDA approval of breast cancer drugs do not meet the ASCO-VF or ESMO-MCBS criteria for substantial clinical benefit. There is substantial inter-framework variability in the assessment of clinical benefit in the curative setting. Over time, there has been a substantial shift towards use of surrogate endpoints as the basis for approval without a clear improvement in substantial clinical benefit.

Optimism bias in the design of phase III randomized control trials (RCTs) evaluating PD-1/PD-L1 targeting monoclonal antibodies (mAbs).

e18616 Background: PD-1/PD-L1 targeting monoclonal antibodies (mAbs) improve outcomes in multiple cancer types. Multiple mAbs are in clinical development, and many randomized control trials (RCTs) have been completed or are in progress. These RCTs compete for limited clinical trials infrastructure, human resources and patients. Since the hypothesized benefit of an intervention is a critical determinant of the number of patients required for an RCT, it is crucial that the expected benefit be estimated appropriately. We examined the hypothesized hazard ratio (HHR) and the observed hazard ratio (OHR) in RCTs evaluating PD-1/PD-L1 targeting mAbs. Methods: Publications of RCTs evaluating at least one PD-1/PD-L1 targeting mAbs approved by the US Food and Drug Administration were identified through PubMed searches. The primary publication for each RCT and its associated protocol were retrieved. Two investigators independently extracted HHR, OHR for the primary endpoint among other data elements. The differences (∆HR) in HHR and OHR were analyzed statistically. Updated OHRs (uOHR) were extracted from reports with extended follow-ups. Results: 49 RCTs enrolling 36867 patients were included. 45/49 RCTs were in the palliative setting. HHR was met or exceeded in 22 (45%) RCTs. The mean HHR and OHR were 0.672 and 0.738, respectively. The mean ∆HR was 0.067 (range: -0.300 to 0.895, 95% confidence interval = 0.003 – 0.130). A lower magnitude of effect than hypothesized in 12/29 RCTs in non-small cell lung cancer, melanoma and renal cell carcinoma, but in 15/20 RCTs in other cancer types. OHR was ≥ 1.0 in 6 RCTs (12%). In the palliative setting, ∆HR was larger in more heavily pre-treated patients. PD-L1 expression was not associated with magnitude of effect. However, a higher magnitude of effect was observed for RCTs published in the New England Journal of Medicine. For 18 RCTs with extended follow-ups, uOHR was higher than OHR in 8. Conclusions: The majority of published RCTs evaluating PD-1/PD-L1 targeting mAbs did not achieve their hypothesized magnitude of effect. Investigators’ optimism regarding these agents should be combined with more realistic expectations. The optimism bias requires attention from the cancer clinical research community given the number of these agents in development and the intense interest in evaluating these agents in various disease settings.