Circulating tumor DNA as a biomarker for predicting progression-free survival and overall survival in patients with epithelial ovarian cancer: a systematic review and meta-analysis.

OBJECTIVES: Circulating tumor DNA (ctDNA) is emerging as a potential prognostic biomarker in multiple tumor types. However, despite the many studies available on small series of patients with ovarian cancer, a recent systematic review and meta-analysis is lacking. The objective of this study was to determine the association of ctDNA with progression-free-survival and overall survival in patients with epithelial ovarian cancer. METHODS: An electronic search was conducted using PubMed (MEDLINE), Embase, CENTRAL (Cochrane Library), and CINAHL-Complete from January 2000 to September 15, 2023. To be included in the analysis the studies had to meet the following pre-specified inclusion criteria: (1) evaluable ctDNA; (2) progression-free-survival and overall survival reported as hazard ratio (HR); and (3) the patient population had epithelial ovarian cancer at the time of ctDNA detection. We evaluated the association of ctDNA with progression-free survival and overall survival. Secondary outcomes focused on sub-group analysis of genomic alterations and international Federation of Gynecology and Obstetrics (FIGO) stage. RESULTS: A total of 26 studies reporting on 1696 patients with epithelial ovarian cancer were included. The overall concordance rate between plasma-based and tissue-based analyses was approximately 62%. We found that a high level of ctDNA in epithelial ovarian cancer was associated with worse progression-free survival (HR 5.31, 95% CI 2.14 to 13.17, p<0.001) and overall survival (HR 2.98, 95% CI 1.86 to 4.76, p<0.0001). The sub-group analysis showed a greater than threefold increase in the risk of relapse in patients with positive HOXA9 meth-ctDNA (HR 3.84, 95% CI 1.57 to 9.41, p=0.003). CONCLUSIONS: ctDNA was significantly associated with worse progression-free survival and overall survival in patients with epithelial ovarian cancer. Further prospective studies are needed. PROSPERO REGISTRATION NUMBER: CRD42023469390.

Cost-effectiveness of pembrolizumab in first-line for microsatellite-instability-high or mismatch-repair-deficient metastatic colorectal cancerF.

The aim of this paper was to assess the cost-effectiveness of pembrolizumab in first-line for microsatellite-instability-high or mismatch-repair-deficient metastatic colorectal cancer. We have considered the pivotal phase III randomized controlled trial of pembrolizumab in first-line for microsatellite-instability-high mismatch-repair-deficient metastatic colorectal cancer. The last available update of each trial was considered as the original source. Incremental cost-effectiveness ratio was calculated as the ratio between the difference of the costs in the intervention and in the control groups (pharmacy costs) and the difference between the effect in the intervention and in the control groups (progression-free survival). The costs of drugs are at the Pharmacy of the Mater Salutis Hospital of Legnago (VR, Italy) and are expressed in euros (€). Three hundred and seven patients were considered in the pivotal phase III randomized controlled trial. Pembrolizumab obtained a cost per month progression-free survival gained ranged from 6471 € towards mFOLFOX (5-FU, oxaliplatin and leucovorin) plus cetuximab to 7886 € towards mFOLFOX. To sum up, combining pharmacological costs of drugs with the measure of efficacy represented by progression-free survival, at the actual prize pembrolizumab cannot be considered cost-effectiveness for first-line treatment for microsatellite-instability-high mismatch-repair-deficient metastatic colorectal cancer. A reduction in pharmacological costs is mandatory.

A Systematic Review and a Meta-analysis of Randomized Controlled Trials' Control Groups in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC).

PURPOSE OF REVIEW: Determining the risk for progression or survival after standard androgen deprivation treatment (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC) is essential for stratifying patients according to expected outcomes in future studies of treatment combination. This systematic review and meta-analysis aims to estimate the progression-free survival (PFS) and overall survival (OS) probabilities in the control group of randomized controlled trials (RCTs) of different regimens of standard androgen deprivation treatment (ADT) in mHSPC and to identify possible predictors of outcomes. RECENT FINDINGS: Studies reporting time-dependent outcomes (progression or death) after standard ADT treatment of mHSPC were searched in MEDLINE, CANCERLIT, the Cochrane Controlled Trials Register, and the Cochrane Library from inception through June 2021. Data on patient populations and outcomes were extracted from each study by three independent observers and combined using a distribution-free summary survival curve. Primary outcomes were actuarial probabilities of disease progression and survival. Fifteen studies met the inclusion criteria. The pooled estimate of the actuarial PFS rate was 35.2% at two years. The pooled actuarial OS rate was 62.5% at three years. Heterogeneity among studies was highly significant for all outcomes. By univariate meta-regression analyses, high-volume disease and the presence of visceral metastases were associated with shorter survival. Our findings show that PFS and OS are highly variable in patients with mHSPC treated with ADT, providing a helpful benchmark for indirect comparisons of the benefits of the combination of chemotherapy and second-generation hormonotherapy.

Cumulative dose, toxicity, and outcomes of spinal metastases re-irradiation : Systematic review on behalf of the Re-Irradiation Working Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

PURPOSE: The aim of this study was to identify patient-, tumor-, or treatment-related factors which may affect disease-related outcomes of re-irradiation (reRT) in patients with previously irradiated vertebral metastases. METHODS: A computerized search of the literature was performed by searching for terms related to reRT and spinal metastases in MEDLINE, EMBASE, OVID, and the Cochrane database from 1995 to 2019. Studies including at least 10 patients who had received reRT at the same site of initial radiotherapy for vertebral metastases with localized external beam radiotherapy were included. To determine the pooled ≥G3 acute and late toxicity rate, pain relief, local control, and overall survival, a meta-analysis technique of single-arm studies was performed. RESULTS: Nineteen studies including 1373 patients met the inclusion criteria for this systematic review. The pooled pain relief, neurological improvement, 1­year local control, and 1­year overall survival rates were 74.3%, 73.8%, 78.8%, and 54.6%, respectively, with moderate to high heterogeneity among studies. No difference in heterogeneity was evidenced for pain relief or local control after omitting studies not using stereotactic body radiotherapy (SBRT) or studies delivering biologically effective dose (BED) < 45 Gy10, whereas heterogeneity for 1­year OS was lower after omitting studies not using SBRT and delivering BED < 45 Gy10. The pooled results of grade ≥ 3 acute and late toxicity were 0.4% (95% confidence interval: 0.1-1.2%) and 2.2% (95% confidence interval: 1.2-37%), respectively, with low heterogeneity among studies. CONCLUSION: While this systematic review confirmed that reRT is both safe and effective for treating patients with recurrent spinal metastases, it could not identify factors which may affect outcomes of reRT in this patient population.

Psoriasis and psoriasiform reactions secondary to immune checkpoint inhibitors.

The advent of Immune Checkpoint Inhibitors (ICIs) as a standard of care for several cancers, including melanoma and head/neck squamous cell carcinoma has changed the therapeutic approach to these conditions, drawing at the same time the attention on some safety issues related to their use. To assess the incidence of psoriasis as a specific immune-related cutaneous adverse event attributing to ICIs using the Eudravigilance reporting system. All reports of adverse drug reactions (ADRs) concerning either exacerbation of psoriasis or de novo onset of psoriasis/psoriasiform reactions associated to the use of Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) inhibitors ipilimumab and tremelimumab, and the Programmed cell Death protein 1/Programmed Death-Ligand 1 (PD-1/PD-L1) inhibitors nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and cemiplimab were identified and extracted from the Eudravigilance reporting system, during the period between the date of market licensing (for each study drug) and 30 October 2020. 8213 reports of cutaneous ADRs associated with at least one of study drug have been recorded, of which 315 (3.8%) reporting psoriasis and/or psoriasiform reactions as ADR. In 70.8% of reports patients had pre-existing disease. ICIs-related skin toxicity is a well-established phenomenon, presenting with several conditions, sustained by an immune background based on the activity of some cells (CD4+/CD8+ T-cells, neutrophils, eosinophils, and plasmocytes), inflammatory mediators, chemokines, and tumor-specific antibodies. In this setting, psoriasis represents probably the most paradigmatic model of these reactions, thus requiring adequate recognition as no guidelines on management are now available.

The role of fentanyl in the treatment of breakthrough cancer pain: Different biotechnologies, different results and different drug costs.

The aim of this paper was to assess the drug costs of the different biotechnologies (intranasal fentanyl spray (INFS), oral transmucosal fentanyl citrate (OTFC) and fentanyl buccal tablet (FBT)) in the treatment of breakthrough cancer pain (BTCP). We have calculated the mean drug costs (expressed in euros (€)) for patients treated for BTCP. INFS resulted the less expensive towards OTFC and FBT, with 697 440 €versus (vs.) 809 552 €vs. 779 662 €every 100 patients treated for BTCP, respectively. In conclusion, combining drug costs of different biotechnologies (INFS, OTFC and FBT) with the measure of efficacy represented by the reduction of BTCP avoided (incremental cost-effectiveness ratio, ICER), INFS resulted in better cost-effectiveness.

Dose-escalation strategy in refractory metastatic colorectal cancer: A change in terms of cost-effectiveness.

The analysis was conducted to assess the pharmacological costs of regorafenib and trifluridine/tipiracil in the treatment of refractory metastatic colorectal cancer (mCRC). Pivotal phase III randomized controlled trials (RCTs) of regorafenib and trifluridine/tipiracil in the treatment of refractory mCRC were considered. We have also considered the ReDOS trial, in order to verify if the dose-escalation strategy (practice changing for regorafenib) could influences the results. Differences in OS (expressed in months) between the different arms were calculated and compared with the pharmacological costs (at the Pharmacy of our Hospital and expressed in euros (€)) needed to get one month of OS. Trifluridine/tipiracil resulted the less expensive, with 1167.50 €per month OS-gained. The ReDOS trial further reduce costs with 510.41 €per month OS-gained in favour of regorafenib with the escalation-dose strategy. Both regorafenib and trifluridine/tipiracil can be considered economically sustainable treatments for refractory mCRC, apparently with a lower cost of trifluridine/tipiracil. The adoption of a dose-escalation strategy (ReDOS trial) could reverse the situation making regorafenib more cost-effective than trifluridine/tipiracil.

Radiotherapy activities and technological equipment in Veneto, Italy: a report from the Rete Radioterapica Veneta.

BACKGROUND: Despite the pivotal role of radiotherapy in oncology, the provision of radiation treatments remains inadequate in many areas of the world. The present report is an assessment conducted among Radiation Oncology centers of Veneto region with the aim to collect information concerning radiotherapy assets and technological equipment availability. METHODS: Data concerning Veneto Radiation Oncology departments about radiotherapy activities, number of treatments, techniques used and radiotherapy machines available were collected. The reference time period was 2018. Reimbursement system databases and business intelligence systems were used. Extra-regional attraction and migration were evaluated. When available, data were compared to previous years. RESULTS: Veneto in 2018 was endowed with 1 megavolt unit for about 153,000 inhabitants. The number of megavolt machines per million inhabitants resulted to be 6.72. In 51% of radiotherapy treatments, intensity-modulated techniques were performed. Six percent of treatments were administered to extra-regional patients. CONCLUSION: Radiotherapy assets and equipment in Veneto seem to be appropriate to standard requests in terms of availability and technology.

Resveratrol as Chemosensitizer Agent: State of Art and Future Perspectives.

Resistance to chemotherapy still remains a major challenge in the clinic, impairing the quality of life and survival rate of patients. The identification of unconventional chemosensitizing agents is therefore an interesting aspect of cancer research. Resveratrol has emerged in the last decades as a fascinating molecule, able to modulate several cancer-related molecular mechanisms, suggesting a possible application as an adjuvant in cancer management. This review goes deep into the existing literature concerning the possible chemosensitizing effect of resveratrol associated with the most conventional chemotherapeutic drugs. Despite the promising effects observed in different cancer types in in vitro studies, the clinical translation still presents strong limitations due to the low bioavailability of resveratrol. Recently, efforts have been moved in the field of drug delivery to identifying possible strategies/formulations useful for a more effective administration. Despite the necessity of a huge implementation in this research area, resveratrol appears as a promising molecule able to sensitize resistant tumors to drugs, suggesting its potential use in therapy-refractory cancer patients.

Role of upper abdominal reirradiation for gastrointestinal malignancies: a systematic review of cumulative dose, toxicity, and outcomes on behalf of the Re-Irradiation Working Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

PURPOSE: Abdominal recurrences of gastrointestinal malignancies are common. Evidence in clinical studies has shown that re-irradiation (Re-I) is tolerable and efficient in different tumor locations. In contrast, little clinical data are available on normal long-term Re­I tolerance doses. A systematic review of upper abdominal Re­I was performed with the aim of exploring the cumulative dose, toxicity, and outcomes. METHODS: A computerized search was undertaken in MEDLINE, EMBASE, OVID, and the Cochrane database. Only studies reporting toxicity and/or outcomes were taken into consideration. To improve the comparability of the different Re­I regimens and assess the relationship between Radiotherapy (RT) dose and toxicity, the equivalent dose in 2­Gy fractions was calculated according to the linear quadratic model. RESULTS: Sixteen studies met the inclusion criteria, with the total patients numbering 408. Median follow-up Re­I ranged from 5.9 to 45 months. The median time elapsed since previous RT treatment was 15 months (2-162 months). Re­I prescription doses were variable (22.5 Gy in 3 fractions to 126.5 Gy with 125I). Cumulative doses calculated for acute- and late-responding tissues ranged from 67.25 to 136 Gy and 30.3 to 188.38 Gy, respectively. Comprehensively, the pooled ≥G3 toxicity was 12% (95%CI: 7.6-19%). The overall 1­year survival and local recurrence-free survival rates were 53.7% (95%CI: 45.6-63.2%) and 66.5% (95% CI: 58.7-75.4%), respectively. Pain improvement was reported in 66.9% of patients. CONCLUSION: Due to limited evidence as a result of the retrospective design of the majority of the studies, our review suggests that upper abdominal Re­I is effective in terms of local control and palliation, with a moderate rate of severe toxicities.

Ten daily fractions for partial breast irradiation. Long-term results of a prospective phase II trial.

Partial breast irradiation (PBI) is an effective adjuvant treatment after breast conservative surgery for selected early-stage breast cancer patients. However, the best fractionation scheme is not well defined. Hereby, we report the 5-year clinical outcome and toxicity of a phase II prospective study of a novel regimen to deliver PBI, which consists in 40 Gy delivered in 10 daily fractions. Patients with early-stage (pT1-pT2, pN0-pN1a, M0) invasive breast cancer were enrolled after conservative surgery. The minimum age at diagnosis was 60 years old. PBI was delivered with 3D-conformal radiotherapy technique with a total dose of 40 Gy, fractionated in 10 daily fractions (4 Gy/fraction). Eighty patients were enrolled. The median follow-up was 67 months. Five-year local control (LC), disease-free survival (DFS), and overall survival (OS) were 95%, 91%, and 96%, respectively. Grade I and II subcutaneous fibrosis were documented in 23% and 5% of cases. No grade III late toxicity was observed. PBI delivered in 40 Gy in 10 daily fractions provided good clinical results and was a valid radiotherapy option for early-stage breast cancer patients.

Pattern of dysphagia after swallowing-sparing intensity-modulated radiotherapy (IMRT) of head and neck cancers: results of a mono-institutional prospective study.

BACKGROUND AND PURPOSE: A prospective instrumental assessment of late dysphagia using swallowing organs at risk (SWOARs)-sparing IMRT for nasopharyngeal and oropharyngeal cancers. MATERIALS AND METHODS: Objective instrumental assessment included fiberoptic endoscopic evaluation of swallowing (FEES) and videofluoroscopy (VFS) at baseline, and at 6 and 12 months after treatment. FEES assessed the pharyngeal residue according to the Farneti pooling score (P-score) as follows: 4-5 no dysphagia; 6-7 mild dysphagia; 8-9 moderate dysphagia; 10-11 severe dysphagia. Three different consistencies were tested for the P­score: liquid (L), semisolid (SS), and solid (S). VFS assessed penetration-aspiration according to the Penetration-Aspiration Scale (PAS) and two different consistencies of the bolus were tested: thin liquid barium (L) and paste barium (S). RESULTS: 38 patients were evaluable. There was a significant worsening of the P­score at 6 months both for SS (p = 0.015) and S (p < 0.001), which persisted only for S at 12 months (p < 0.0001). Similarly, there was a significant worsening of the PAS score at 6 and 12 months (p = 0.065 and 0.039, respectively) for the S bolus. Overall, 3-7 and 10-14% aspiration after L and S was observed, respectively. CONCLUSIONS: Promising results using a SWOARs-sparing IMRT technique are reported. Therefore, treatment plans should be optimized for reducing doses to these structures.

Nomegestrol acetate/estradiol hormonal oral contraceptive and breast cancer risk.

Combined hormonal contraceptives (CHCs) contain estrogen and progestin, which can stimulate estrogen-sensitive and/or progesterone-sensitive breast cancer growth. Until recently, ethinylestradiol had been almost the only estrogen used for decades, and its dose has been greatly reduced over time. The first generations of birth control pills contained approximately five times more estrogen and four times more progestin than the latest contraceptives. Newer CHCs also contain steroids that more closely mimic the physiological estradiol (E2) and progesterone effects. The newer CHC formulations are thus expected to have less influence on the breast, although it is very difficult to demonstrate any difference among the recent available preparations in human studies. Recently, nomegestrol acetate (NOMAC), a neutral, nonandrogenic, progesterone-like profile progestin, has become available in combination with the 'natural' estrogen, E2. According to the literature, NOMAC/E2 is expected to have either a lesser stimulating effect or a neutral effect on estrogen-sensitive breast cancers. We performed an analysis of the available studies and a bibliographical review. The endocrine and metabolic effects of NOMAC/E2 formulation might lead to a lesser breast tissue stimulation. The data reported, confirmed through clinical studies, should be considered when choosing a hormonal contraceptive, especially when breast stimulation is a concern.

Treatment options in first-line metastatic renal carcinoma: A meta-analysis of 2556 patients treated with immune checkpoint inhibitors-based combinations in randomised controlled trials.

BACKGROUND & AIMS: The average five-year survival of metastatic renal cell carcinoma (mRCC) is 71%. However, there is significant variability in patient prognosis. Immune checkpoint inhibitors (ICIs) have been introduced into the treatment landscape of mRCC. This meta-analysis aimed to estimate progression-free and overall survival probabilities and identify possible outcome predictors of mRCC patients treated with ICI combination as first-line treatment. METHODS: Studies comparing the combination of ICI combinations versus standard of therapy for first-line treatment of advanced renal-cell carcinoma were searched in MEDLINE, CANCERLIT, the Cochrane Controlled Trials Register, and the Cochrane Library from inception through September 2023. Data on patient populations and outcomes were extracted from each study by three independent observers and combined using the DerSimonian and Laird methods. RESULTS: Six studies met the inclusion criteria. Globally, 5121 patients were included in this meta-analysis: 2556 patients treated with immune checkpoint inhibitors and 2565 with sunitinib as control. The ICI combination was associated with improved PFS (hazard ratio (HR) 0.68; 95 % confidence interval (CI), 0.56-0.81, p < 0.0001). Furthermore, ICI combination was also associated with OS improvement (HR 0.85; 95 % CI, 0.78-0.92, p = 0.001). There is no statistical increase in adverse events. CONCLUSIONS: Our findings show that PFS and OS are statistically increased in mRCC with ICI combination treatment by 32% and 15%, respectively.

Further Clarification of Pain Management Complexity in Radiotherapy: Insights from Modern Statistical Approaches.

BACKGROUND: The primary objective of this study was to assess the adequacy of analgesic care in radiotherapy (RT) patients, with a secondary objective to identify predictive variables associated with pain management adequacy using a modern statistical approach, integrating the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and the Classification and Regression Tree (CART) analysis. METHODS: This observational, multicenter cohort study involved 1387 patients reporting pain or taking analgesic drugs from 13 RT departments in Italy. The Pain Management Index (PMI) served as the measure for pain control adequacy, with a PMI score < 0 indicating suboptimal management. Patient demographics, clinical status, and treatment-related factors were examined to discern the predictors of pain management adequacy. RESULTS: Among the analyzed cohort, 46.1% reported inadequately managed pain. Non-cancer pain origin, breast cancer diagnosis, higher ECOG Performance Status scores, younger patient age, early assessment phase, and curative treatment intent emerged as significant determinants of negative PMI from the LASSO analysis. Notably, pain management was observed to improve as RT progressed, with a greater discrepancy between cancer (33.2% with PMI < 0) and non-cancer pain (73.1% with PMI < 0). Breast cancer patients under 70 years of age with non-cancer pain had the highest rate of negative PMI at 86.5%, highlighting a potential deficiency in managing benign pain in younger patients. CONCLUSIONS: The study underscores the dynamic nature of pain management during RT, suggesting improvements over the treatment course yet revealing specific challenges in non-cancer pain management, particularly among younger breast cancer patients. The use of advanced statistical techniques for analysis stresses the importance of a multifaceted approach to pain management, one that incorporates both cancer and non-cancer pain considerations to ensure a holistic and improved quality of oncological care.

Sorafenib for the treatment of unresectable hepatocellular carcinoma in HIV-positive patients.

Few data are available on the safety and efficacy of sorafenib in HIV-infected patients with unresectable hepatocellular carcinoma (HIV-u-HCC) and concomitant highly active antiretroviral therapy (HAART). Between July 2007 and October 2010, 27 consecutive HIV-u-HCC patients were treated with sorafenib and concomitant HAART within the Gruppo Italiano Cooperativo AIDS e Tumori (GICAT). Three patients achieved a partial response, 12 achieved a stable disease, and 12 showed progression. The median time to progression and overall survival was 5.1 (range 0.5-13.3) and 12.8 (range 1.1-23.5) months, respectively. Grades 3-4 toxicities included diarrhea (four patients, 14.8%), hypertension (three patients, 11%), and hand-and-foot skin reaction (four patients, 14.9%). Most drug-related side effects were low grade and manageable. This retrospective study shows favorable survival data among HIV-u-HCC patients treated with sorafenib together with a reasonable safety profile.

Loss of Primary Cilia Potentiates BRAF/MAPK Pathway Activation in Rhabdoid Colorectal Carcinoma: A Series of 21 Cases Showing Ciliary Rootlet CoiledCoil (CROCC) Alterations.

A rhabdoid colorectal tumor (RCT) is a rare cancer with aggressive clinical behavior. Recently, it has been recognized as a distinct disease entity, characterized by genetic alterations in the SMARCB1 and Ciliary Rootlet Coiled-Coil (CROCC). We here investigate the genetic and immunophenotypic profiling of 21 RCTs using immunohistochemistry and next-generation sequencing. Mismatch repair-deficient phenotypes were identified in 60% of RCTs. Similarly, a large proportion of cancers exhibited the combined marker phenotype (CK7-/CK20-/CDX2-) not common to classical adenocarcinoma variants. More than 70% of cases displayed aberrant activation of the mitogen-activated protein kinase (MAPK) pathway with mutations prevalently in BRAF V600E. SMARCB1/INI1 expression was normal in a large majority of lesions. In contrast, ciliogenic markers including CROCC and γ-tubulin were globally altered in tumors. Notably, CROCC and γ-tubulin were observed to colocalize in large cilia found on cancer tissues but not in normal controls. Taken together, our findings indicate that primary ciliogenesis and MAPK pathway activation contribute to the aggressiveness of RCTs and, therefore, may constitute a novel therapeutic target.

PML at mitochondria-associated membranes governs a trimeric complex with NLRP3 and P2X7R that modulates the tumor immune microenvironment.

Uncontrolled inflammatory response arising from the tumor microenvironment (TME) significantly contributes to cancer progression, prompting an investigation and careful evaluation of counter-regulatory mechanisms. We identified a trimeric complex at the mitochondria-associated membranes (MAMs), in which the purinergic P2X7 receptor - NLRP3 inflammasome liaison is fine-tuned by the tumor suppressor PML. PML downregulation drives an exacerbated immune response due to a loss of P2X7R-NLRP3 restraint that boosts tumor growth. PML mislocalization from MAMs elicits an uncontrolled NLRP3 activation, and consequent cytokines blast fueling cancer and worsening the tumor prognosis in different human cancers. New mechanistic insights are provided for the PML-P2X7R-NLRP3 axis to govern the TME in human carcinogenesis, fostering new targeted therapeutic approaches.

Adequacy of Pain Management in Patients Referred for Radiation Therapy: A Subanalysis of the Multicenter ARISE-1 Study.

BACKGROUND: Pain is a prevalent symptom among cancer patients, and its management is crucial for improving their quality of life. However, pain management in cancer patients referred to radiotherapy (RT) departments is often inadequate, and limited research has been conducted on this specific population. This study aimed to assess the adequacy and effectiveness of pain management when patients are referred for RT. Moreover, we explored potential predictors of adequate pain management. METHODS: This observational, prospective, multicenter cohort study included cancer patients aged 18 years or older who were referred to RT departments. A pain management assessment was conducted using the Pain Management Index (PMI), calculated by subtracting the pain score from the analgesic score (PMI < 0 indicated inadequate pain management). Univariate and multivariate analyses were performed to identify predictors of adequate pain management. RESULTS: A total of 1042 cancer outpatients were included in the study. The analysis revealed that 42.9% of patients with pain did not receive adequate pain management based on PMI values. Among patients with pain or taking analgesics and referred to palliative or curative RT, 72% and 75% had inadequate or ineffective analgesic therapy, respectively. The odds of receiving adequate pain management (PMI ≥ 0) were higher in patients undergoing palliative RT (OR 2.52; p < 0.001), with worse ECOG-PS scores of 2, 3 and 4 (OR 1.63, 2.23, 5.31, respectively; p: 0.017, 0.002, 0.009, respectively) compared to a score of 1 for those with cancer-related pain (OR 0.38; p < 0.001), and treated in northern Italy compared to central and southern of Italy (OR 0.25, 0.42, respectively; p < 0.001). CONCLUSIONS: In this study, a substantial proportion of cancer patients referred to RT departments did not receive adequate pain management. Educational and organizational strategies are necessary to address the inadequate pain management observed in this population. Moreover, increasing the attention paid to non-cancer pain and an earlier referral of patients for palliative RT in the course of the disease may improve pain response and treatment outcomes.