Adverse event profile for immunotherapy agents compared with chemotherapy in solid organ tumors: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Immunotherapy agents are an innovative oncological treatment modality and as a result their use has expanded widely. Understanding the treatment-related adverse events (AEs) of these drugs compared with traditional chemotherapy is crucial for clinical practice. DESIGN: A systematic review of studies indexed in Medline (PubMed), Embase, Web of Science, and the Cochrane Databases from January 2000 to 14 February 2019 was conducted. Randomized clinical trials comparing immunotherapy [cytotoxic T-lymphocyte protein-4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed death-ligand 1 (PD-L1)] with standard-of-care chemotherapy in the treatment of advanced solid-organ neoplasms were included if AEs were reported as an outcome. Primary outcome was AEs ≥ grade 3 in severity. Secondary outcomes were proportion of overall AEs, treatment discontinuation due to AEs, deaths due to AEs, and specific AEs [fatigue, diarrhea, acute kidney injury (AKI), colitis, pneumonitis, and hypothyroidism]. Paule-Mandel pooling and a random effects model were used to produce odds ratios (ORs) for measures of effects. RESULTS: Among 10 598 abstracts screened, we included 22 studies involving 12 727 patients. In the immunotherapy group, 16.5% of patients developed an AE ≥ grade 3 in severity, compared with 41.09% in the chemotherapy arm [OR = 0.26, 95% confidence interval (CI) 0.19-0.35, I2 = 92%]. Patients receiving immunotherapy also had lower odds of developing an AE overall (OR = 0.35, 95% CI 0.28-0.44; I2 = 77%), terminating therapy due to an AE (OR = 0.55, 95% CI 0.39-0.78, I2 = 80%), or dying from a treatment-related AE (OR = 0.67, 95% CI 0.46-0.98, I2 = 0%). When treated with chemotherapy versus immunotherapy, patients more frequently experienced fatigue (25.10% versus 15.83%), diarrhea (14.97% versus 11.13%), and AKI (1.79% versus 1.31%). However, colitis (1.02% versus 0.26%), pneumonitis (3.36% versus 0.36%), and hypothyroidism (6.82% versus 0.37%) were more common in those treated with immunotherapy. CONCLUSIONS: Treatment of advanced solid-organ malignancies with immunotherapy compared with traditional chemotherapy is associated with a lower risk of AEs.

Doctor, what are my options? A prospective cohort study of an individualized care plan for patients with gastrointestinal cancer.

BACKGROUND: For cancer patients, information about their disease and its treatment is often delivered within a short time period, potentially leading to patient misunderstanding, which can impede optimal patient care. In this 3-part clinical study, we investigated the utility of an individualized care plan for patients with gastrointestinal (gi) cancer starting a new treatment. METHODS: In part 1, a comprehensive literature search identified items for potential inclusion in the care plan. Those items were formatted into a questionnaire. The questionnaire was then administered to patients as a structured interview. In part 2, health care professionals involved in the care of patients with gi cancer evaluated the resulting care plan for content and relevancy. In part 3, a 20-week prospective cohort study (10 weeks using standard of care, 10 weeks using individualized care plans) was conducted. Outcomes were assessed at baseline and at 2-4 weeks after administration of the care plan. RESULTS: In part 1, a 73-item questionnaire was developed and completed by 20 patients in semi-structured interviews. In part 2, long and short versions of the care plan were created. Most health care professionals preferred the long version. Based on their comments, a final version of the care plan was created. The part 3 study enrolled 104 patients. Overall satisfaction scores were significantly higher in the intervention group at baseline (p = 0.010) and follow-up (p = 0.005). Compared with control patients, the intervention cohort also reported significantly higher overall quality of life (p = 0.044) and fewer symptoms of anxiety (p = 0.048) at follow-up. CONCLUSIONS: Provision of an individualized care plan resulted in improvements in outcome measures at both baseline and follow-up. Future studies are needed to confirm these findings.

Change in urinary markers of osteoclast activity following palliative radiotherapy for bone metastases.

AIMS: To examine the effect of radiotherapy for bone metastases on urinary markers of osteoclast activity. MATERIALS AND METHODS: Patients with radiological evidence of bone metastases planned for palliative radiotherapy were eligible for the study. A urine specimen was collected before and 1 month after radiotherapy to assess levels of calcium, creatinine, magnesium, phosphate, N-telopeptide and pyridinoline. The Brief Pain Inventory was completed in person at baseline and by telephone follow-up at 1 month after radiotherapy. Patients were classified as responders (complete or partial pain response) or non-responders (stable or progressive pain) to radiotherapy based on the International Bone Metastases Consensus Criteria for end point measurements. Absolute values of urine markers were compared between responders and non-responders, or between responders and patients with progression. RESULTS: Our study population consisted of 74 men and 51 women. A single 8 Gy or 20 Gy in five daily fractions were commonly employed. At the 1 month follow-up, all Brief Pain Inventory functional interference scores showed a highly significant decrease from baseline (P<0.01). From our study population, 58 (64%) were classified as responders and 57 (46%) as non-responders to radiotherapy. We compared the urinary markers between the responders and the non-responders. There were no statistically significant differences between the two groups either in terms of baseline markers or in terms of month 1 follow-up markers. There was no significant change from baseline to the 1 month follow-up in responders or in non-responders to radiotherapy. CONCLUSION: Baseline levels of urinary markers could not predict which patient would benefit from palliative radiotherapy.

Dexamethasone for the prophylaxis of radiation-induced pain flare after palliative radiotherapy for symptomatic bone metastases: a phase II study.

AIMS: Pain flare occurs in over one-third of patients receiving palliative radiotherapy for bone metastases. A single dose of dexamethasone can decrease the incidence of pain flare during the first 2 days immediately after radiotherapy. We conducted a phase II prospective study to investigate the prophylactic role of prolonged dexamethasone. MATERIALS AND METHODS: Patients with bone metastases treated with a single 8Gy were prescribed 8mg dexamethasone just before palliative radiotherapy and for 3 consecutive days after treatment. Worst pain score and analgesic consumption data were collected at baseline and daily for 10 days after treatment. Analgesic consumption was converted into a total daily oral morphine equivalent dose in the analysis. Pain flare was defined (a priori) as a two-point increase in worst pain on an 11-point numeric rating scale compared with baseline with no decrease in analgesic intake, or a 25% increase in analgesic intake with no decrease in worst pain score. To distinguish pain flare from progressive disease, we required that the worst pain score and analgesic intake returned to baseline levels after the increase/flare. RESULTS: Forty-one patients were evaluable (32 men, nine women). Their median age was 67 years. The overall incidence of pain flare was 9/41 (22%) within 10 days after the completion of radiotherapy. Most (55%) of these pain flares occurred on day 5. Absence of pain flare was 34/41(83%) and 39/41 (95%) for days 1-5 and 6-10 after the completion of radiotherapy, respectively. CONCLUSION: Dexamethasone is effective in the prophylaxis of radiotherapy-induced pain flare after palliative radiotherapy for bone metastases. Randomised studies are needed to confirm this finding.

Brain metastasis from an unknown primary, or primary brain tumour? A diagnostic dilemma.

Brain metastasis is increasingly common, affecting 20%-40% of cancer patients. After diagnosis, survival is usually limited to months in these patients. Treatment for brain metastasis includes whole-brain radiation therapy, surgical resection, or both. These treatments aim to slow progression of disease and to improve or maintain neurologic function and quality of life.Although less common, primary brain tumours produce symptoms that are similar to those of brain metastasis. Glioblastoma, the most common malignant tumour of the brain, has a median survival of less than 12 months. Patients are often treated with surgical resection followed by radical radiation therapy and chemotherapy.Here, we present 2 separate cases of lesions in the brain radiologically compatible with brain metastasis. In both cases, no primary cancer site had been established, and neurosurgical intervention was sought to obtain a pathologic diagnosis. Both cases were pathologically confirmed as glioblastoma. These cases demonstrate the importance of differentiation between brain metastases and primary brain tumours to ensure that the appropriate management strategy is implemented.

Quality of life in brain metastases radiation trials: a literature review.

BACKGROUND: An estimated 20%-40% of cancer patients will develop brain metastases. Whole-brain radiotherapy (WBRT) is the standard treatment for patients with brain metastases. Although WBRT can reduce neurologic symptoms, the median survival following WBRT is between 3 and 6 months. Given this limited survival, it is important to consider quality of life (QOL) when treating patients with brain metastases. However, few studies have focused on QOL and improvement in patient-rated symptoms as primary outcomes. OBJECTIVE: For an accurate measurement of the extent to which previous trials have utilized QOL tools to evaluate the efficacy of WBRT for treatment of brain metastases, we undertook a literature review to examine the common endpoints and QOL instruments used. METHODS: We conducted a systematic search using the medline (1950 to December 2007) and Cochrane Central Register of Controlled Trials (4th quarter 2007) databases. Eligible studies investigated WBRT in one of the study arms. The following outcomes were included: median survival, overall survival, neurologic function, 1-year local control, and overall response; use of QOL instruments, performance status scales, and neurologic function assessments; and use of other assessment tools. Patient-rated QOL instruments were defined as those that strove to assess all dimensions of QOL; observer-rated performance instruments such as the Karnofsky performance status (kps) were deemed to be performance scales. RESULTS: We identified sixty-one trials that included WBRT as a treatment for brain metastases. Of these sixty-one trials, nine evaluated the treatment of a single brain metastasis, and fifty-two evaluated the treatment of multiple brain metastases. Although fifty-five of the trials employed a QOL instrument, few trials focused on QOL as an outcome. We found 23 different instruments used to evaluate QOL. The most commonly employed instrument was the kps (n = 33), followed by various neurologic function classification scales (n = 21). A preponderance of the studies used 1 (n = 26, 43%) or 2 (n = 21, 34%) QOL instruments. A total of fourteen published trials on brain metastases included an evaluation of the study population's QOL. Those trials included three that used the Functional Assessment of Cancer Therapy-General scale and Brain subscale instrument, three that used the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (C30) and the Brain Cancer Module 20 instrument, two that used study-designed QOL instruments, one that used the Edmonton Symptom Assessment Scale, two that used the Spitzer Quality of Life index, and three that used the kps to evaluate QOL. Some trials reported deterioration in QOL after WBRT in patients with poorer prognosis; other trials detected an improvement in QOL after WBRT in patients with better prognosis. CONCLUSIONS: To date, fourteen trials in brain metastases that have included an evaluation of the study population's QOL have been published. Although some studies showed that certain parameters of QOL deteriorate after WBRT, other studies showed that QOL in patients with better prognosis is improved after WBRT. Because a standard, validated QOL instrument has not been used for this patient population, a comparison of findings concerning QOL between the studies is difficult. The present review emphasizes the need to include QOL measures in future WBRT clinical trials for brain metastases.

Validation of symptom clusters in patients with metastatic bone pain.

PURPOSE: Symptom clusters (scs) are a dynamic construct. They consist of at least 2 or 3 interrelated symptoms that may be a significant predictor of patient morbidity. In a previous study, we identified 2 scs in patients with bone metastases: An activity-related interference cluster, psychology-related interference cluster. These scs may be clinically important in the pain and symptom management of patients with metastatic bone pain. It is therefore important to validate the reported scs to determine if they hold true across similar patient populations. PATIENTS AND METHODS: From February to September 2007, our study accrued 52 patients with bone metastases [29 men (56%), 23 women (44%); median age: 68.5 years (range: 39-87 years)] who were referred for palliative radiotherapy (rt). Prostate (31%), breast (29%), and lung (19%) were the most common primary cancer sites. Treatment arms ranged from single to multiple fractions, with most patients receiving a single 8-Gy fraction (77%) or 20 Gy in 5 fractions (21%). The most prevalent sites for rt were spine (42%), hips (17%), and pelvis (14%). Worst pain at the site of rt and functional interference scores were assessed using the Brief Pain Inventory (BPI), a multidimensional pain instrument that uses 11-point numeric rating scales. Patients provided their symptom severity scores on the BPI at baseline and at 4, 8, and 12 weeks post rt. At all time points, a principal component analysis with varimax rotation was performed on 8 items (worst pain and 7 functional interference items) to determine relationships between symptoms before and after rt for bone pain. RESULTS: Two scs were identified. Cluster 1 included worst pain and interference with general activity, normal work, and walking ability; cluster 2 consisted of interference with mood, sleep, enjoyment of life, and relations with others. Our statistical analysis produced varied results for the 2 clusters found in our previous investigation. These differences may be an indicator for the instability of scs or may be a result of the fewer number of patients accrued in the present validation study. CONCLUSIONS: The scs in our two studies were not identical for patients receiving palliative rt for symptomatic bone metastases. Another sc validation study should be conducted with a larger sample before a conclusion is drawn about the existence of an unstable phenomenon in sc research.

After radiotherapy, do bone metastases from gastrointestinal cancers show response rates similar to those of bone metastases from other primary cancers?

PURPOSE: Reports investigating whether the response rates to palliative radiation therapy (RT) for painful bone metastases from gastrointestinal (GI) cancers are similar to rates for bone metastases from other primary cancer sites have been limited. The present study evaluated response rates for symptomatic bone metastases from gi cancers after palliative outpatient rt in the Rapid Response Radiotherapy Program (RRRP). PATIENTS AND METHODS: We identified 69 patients with bone metastases from gi primaries who received palliative rt in the RRRP clinic during 1999-2006. We extracted records for 31 of these patients during 1999-2003 from an RRRP database that used the Edmonton Symptom Assessment Scale (ESAS). Record for the remaining 38 patients during 2003-2006 were extracted from an RRRP database that used the Brief Pain Inventory (BPI). Eligibility criteria for encryption in the two RRRP databases and for collection of patient demographic information (age, sex, primary cancer site, and Karnofsky performance status) were identical. Response rates for this cohort of metastatic gi patients were then compared to rates for 479 patients receiving palliative RT for bone metastases from other primary cancer sites. Pain scores from the ESAS and BPI and data on analgesic consumption were collected at baseline and by telephone follow-up at 4, 8, and 12 weeks after RT for all patients. Complete (CR), partial (PR), and overall (CR+PR) responses were evaluated according to International Consensus Endpoints. RESULTS: Assessment of the 69 patients with metastatic GI cancers revealed CR, PR, and CR+PR rates of 18%, 42%, and 61% at 4 weeks; 22%, 35%, and 57% at 8 weeks; and 50%, 21%, and 71% at 12 weeks for evaluable patients. The 479 evaluable patients with metastatic cancer from other primary cancer sites had CR, PR, and CR+PR rates of 25%, 27%, and 51% at 4 weeks; 26%, 22%, and 48% at 8 weeks; and 22%, 29%, and 51% at 12 weeks. No statistically significant differences were observed in RT response rates for bone metastases from GI cancers than from other primary cancer sites. CONCLUSIONS: After palliative RT, bone metastases from gi cancers demonstrate response rates that are similar to rates for metastases from other primary cancer sites. Patients with symptomatic bone metastases from GI malignancies should be referred for palliative RT as readily as patients with osseous metastases from other primary cancer sites.

Radiation recall dermatitis: case report and review of the literature.

"Radiation recall"-also called "radiation recall dermatitis"-has been defined as the "recalling" by skin of previous radiation exposure in response to the administration of certain response-inducing drugs. Although the phenomenon is relatively well known in the medical world, an exact cause has not been documented. Here, we report a rare occurrence of the radiation recall phenomenon in a breast cancer patient after palliative radiotherapy for bone, brain, and orbital metastases.