Intrathecal cervical analgesia for cancer pain: a 12-year follow-up study in a comprehensive cancer center.

BACKGROUND: Intrathecal analgesia plays a key role for patients suffering refractory cancer pain. Nevertheless, intrathecal drug delivery systems (IDDS), requiring a cervical catheter tip implantation, have been poorly described in medical literature. AIMS: A monocentric retrospective follow-up study was designed to evaluate results of cervical IDDS for cancer pain. PATIENTS AND METHODS: From January 2010 to December 2022, all intrathecal-treated patients were prescribed a combined intrathecal analgesics regimen through a catheter placed in the cervical vertebral canal. Post-implant assessment of pain was determined using a numeric rating scale (NRS). Patients were followed via day-hospital visits and telephone calls at least monthly. Pain scores were compared using the Wilcoxon's signed rank test. RESULTS: Ninety-eight patients were included in this study; all received intrathecal treatments. Implanted patients suffered from severe pain (mean presurgical maximum numerical rating score 8.02±0.24 despite a mean 562.56±127.72 mg of oral morphine equivalent daily dose). Mean survival time after intrathecal treatment start was 208.48±67 days. Intrathecal drug delivery systems provided pain relief compared with initial pain score with a significant statistical difference after 1 week, 1 month, 2 and 3 months (p<0.01). A 50% reduction in initial pain level was achieved in 93% of cases during the first week of intrathecal implant. CONCLUSIONS: Results suggest that long-term intrathecal treatment using a multidrug regimen for cancer-related pain through cervical intrathecal catheters was suitable and safe in our study population. We demonstrated a clinically and statistically significant pain reduction in patients using mainly a percutaneous lumbar approach.

Correction: Bienfait et al. Evaluation of 8% Capsaicin Patches in Chemotherapy-Induced Peripheral Neuropathy: A Retrospective Study in a Comprehensive Cancer Center. Cancers 2023, 15, 349.

In the original publication [...].

Evaluation of 8% Capsaicin Patches in Chemotherapy-Induced Peripheral Neuropathy: A Retrospective Study in a Comprehensive Cancer Center.

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is often painful and can arise during or after the end of oncological treatments. They are mostly induced by platinum salts, taxanes, and immunotherapies. Their incidence is estimated between 19 and 85%. They can require a chemotherapy dose reduction or early termination. The European Society for Medical Oncology (ESMO) recommends high-concentration capsaicin patch (HCCP) in second line for the treatment of painful CIPN. This treatment induces a significative pain relief but only shown by low-powered studies. The objective of this study was to evaluate efficacy and tolerability of HCCP applications in CIPN. Methods: This monocentric observational retrospective real-world-data study of the CERCAN cohort took place in the Western Cancer Institute's Anaesthesiology and Pain Department at Angers, France. Independent pain physicians completed the CGIC (Clinician Global Impression of Change) for each patient who benefited from HCCP applications for painful CIPN starting from 1 January 2014 to 22 December 2021, based on the collected data after every patch application. Results: A total of 57 patients (80.7% women) was treated with HCCP for painful CIPN, and 184 applications were realized, consisting of 296 sessions. CGIC found an important or complete pain relief for 61 applications (33.2%, corresponding to 43.9% patients). We found less efficacy for platinum-salts-induced CIPN compared to others (p = 0.0238). The efficacy was significatively higher for repeated applications when HCCP was used in second line compared to third line (p = 0.018). The efficacy of HCCP was significatively higher starting the third application (p = 0.0334). HCCPs were mainly responsible for local adverse events found in 66.6% patients (65.1% burning or painful sensation, 21.1% erythema). Conclusion: HCCP applications in painful CIPN induce an important pain relief with a global satisfying tolerability.

Unresolved early post-operative pain trajectory predicts moderate-to-severe persistent pain after breast cancer surgery-An observational cohort study.

BACKGROUND: Modelling acute post-operative pain trajectories may improve the prediction of persistent pain after breast cancer surgery (PPBCS). This study aimed to investigate the predictive accuracy of early post-operative pain (EPOP) trajectories in the development of PPBCS. MATERIALS & METHODS: This observational study was conducted in a French Comprehensive Cancer Centre and included patients who underwent breast cancer surgery from December 2017 to November 2018. Perioperative and follow-up data were obtained from medical records, and anaesthesia and perioperative charts. EPOP was defined as pain intensity during the first 24 h after surgery, and modelled by a pain trajectory. K-means clustering method was used to identify patient subgroups with similar EPOP trajectories. The prevalence of moderate-to-severe PPBCS (numeric rating scale ≥4) was evaluated until 24 months after surgery. RESULTS: A total of 608 patients were included in the study, of which 18% (n = 108) and 9% (n = 52) reported mild and moderate-to-severe PPBCS, respectively. Based on EPOP trajectories, we were able to identify a low (64%, n = 388), resolved (30%, n = 182), and unresolved (6%, n = 38) pain group. Multivariate analysis identified younger age, axillary lymph node dissection, and unresolved EPOP trajectory as independent risk factors for moderate-to-severe PPBCS development. When compared to patients reporting mild PPBCS, moderate-to-severe PPBCS patients experienced significantly more neuropathic pain features, pain-related interference, and delayed opioid cessation. CONCLUSION: EPOP trajectories can distinguish between resolved and unresolved acute pain after breast cancer surgery, allowing early identification of patients at risk to develop significant PPBCS.

Impact of Iron-Deficiency Management on Quality of Life in Patients with Cancer: A Prospective Cohort Study (CAMARA Study).

BACKGROUND: Iron deficiency (ID) is very common in patients with solid tumors and may cause symptoms such as fatigue. However, its impact on clinical outcomes is poorly described. The aim of this prospective monocentric cohort study was to evaluate the evolution of quality of life (QoL) of these patients after iron supplementation. METHODS: We included patients treated for a solid tumor, which were diagnosed with a functional (ferritin <800 ng/mL) or absolute (ferritin <300 ng/mL) ID (transferrin saturation coefficient <20%). The primary endpoint was patients' QoL evolution between baseline and intermediate visit, 15-30 days after initial intravenous iron supplementation, assessed by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale. Secondary endpoints were the same assessment between baseline, intermediate, and final visit at 6 months and the evolution of functional capacities. RESULTS: From 02/2014 to 12/2016, 248 patients were enrolled, of whom 186 were included in the analyses, including 140/186 (75.3%) with absolute ID. Anemia was detected in 141/174 (81.0%) patients at baseline. The FACT-An scores improved significantly between inclusion and intermediate visit (P = .001) and also between the 3 times of evaluation (P < .001). The most improved dimensions were those assessing physical, emotional well-being, and fatigue. Patients who performed the functional tests in all 3 phases had a significant improvement in performance on the majority of tests. CONCLUSION: The supplementation of ID was associated with an improvement of the QoL and functional capacities in patients with cancer. A randomized control trial is necessary to confirm our results. Our findings underline the importance of supportive care, including screening for ID, in oncology. CLINICAL TRIAL REGISTRATION NUMBER: NCT03625661.

Peripheral Neuropathic Pain Following Breast Cancer: Effectiveness and Tolerability of High-Concentration Capsaicin Patch.

PURPOSE: Data supporting the use of high-concentration capsaicin patches (HCCPs) in breast cancer (BC) patients and BC survivors (BCSs) with peripheral neuropathic pain (PNP) are limited. This observational study evaluated the effectiveness and safety of HCCP applications in BCSs/BC patients with PNP. PATIENTS AND METHODS: Data from all patients treated with HCCP in the pain department of a French comprehensive cancer centre were collected from 01-Jan-2014 to 14-Oct-2020. Independent pain specialists completed the Clinical Global Impression of Change (CGIC) for each included patient based on data extracted from patient's electronic medical record compiled by the treating pain specialist after each HCCP application. RESULTS: Patients (N=279; mean age: 59.2 years; previous history of PNP medication: 54.5%) received on average 4.1 repeated HCCP applications (1141 HCCP applications); 68.8% received HCCP as an add-on to systemic therapy and 27.9% as first-line therapy. PNP was most frequently caused by surgery (62.4%) followed by chemotherapy (11.8%) and radiotherapy (6.5%). A complete or important analgesic effect was reported at least once by 82.3% of patients. A 6.0% reported no effect at all. For post-surgical PNP existing for <12 months and >10 years an important or complete effect was observed for 70.7% and 56.0% of applications. For chemotherapy- or radiotherapy-induced PNP, this important or complete effect was observed for 52.7% and 52.3% of applications, respectively. HCCP application was associated with site reactions in 54.4% of patients (mainly burning sensation or pain, 45.9%, or erythema, 30.8%) and high blood pressure in 7.2%. CONCLUSION: This real-world chart review provides important effectiveness and safety information to clinicians when considering topical options to treat PNP in BCSs/BC patients.

Preventing Post Dural Puncture Headache after Intrathecal Drug Delivery System Implantation Through Preventive Fibrin Glue Application: A Retrospective Study.

BACKGROUND: Cerebrospinal fluid (CSF) leakage resulting in post dural puncture headache (PDPH) is a frequent adverse effect observed after intrathecal drug delivery system (IDDS) implantation. CSF leakage symptoms negatively affect patient quality of life and can result in additional complications. Fibrin glue was used to treat CSF leakage syndrome. We developed a procedure to reduce the incidence of PDPH by preventing CSF leakage with the use of fibrin glue during surgery. OBJECTIVES: The main outcome criterion for this study was the incidence of PDPH syndrome after IDDS implantation with or without preventive fibrin glue application during the procedure. STUDY DESIGN: We designed a monocentric retrospective cohort study to compare the incidence of PDPH due to CSF leakage syndrome after lumbar puncture in patients with an implanted intrathecal pump, with or without preventive fibrin glue application during the procedure. SETTING: The study was held in the Anesthesiology and Pain department of the  Integrative Cancer Institute (ICO), Angers - France. METHODS: The study compared 2 patient cohorts over 2 successive periods. Fibrin glue was injected into the introducer needle puncture pathway after placement of the catheter immediately following needle removal. RESULTS: The no-glue group included 107 patients, whereas the glue group included 92 patients.Two application failures were observed (2.04%). Fibrin glue application results in a significant decrease in PDPH incidence, from 32.7% in the no-glue group to 10.92 % (P < 0.001) in the glue group. In regard to severity, in the no-glue group, 37.1% of PDPH syndromes were mild, 34.3% were moderate, and 28.6% were severe. In the fibrin glue group, 80% of PDPH syndromes were mild, and 20% were moderate. No severe PDPHs were reported after fibrin glue application. Duration of symptoms was also statistically shorter in the fibrin glue group (maximum of 3 days vs. 15 days in the no-glue group). In a univariate analysis, preventive fibrin glue application and age are significant to prevent PDPH. In multivariate analysis, only fibrin glue application was statistically significant (odds ratio, 0.26; P = 0.0008). No adverse effects linked to fibrin glue were observed. LIMITATIONS: The main limitation of this study is its retrospective nature. In addition, this study is from a single center with a potential selection bias and a center effect. CONCLUSIONS: The novel use of fibrin glue is promising in terms of its effect on PDPH and its safety profile. Its moderate cost and reproducibility make it an affordable and efficient technique.

R-DHA-oxaliplatin (R-DHAOx) versus R-DHA-cisplatin (R-DHAP) regimen in B-cell lymphoma treatment: A eight-year trajectory study.

BACKGROUND: The R-DHAP regimen (rituximab, cisplatin, dexamethasone, and high-dose cytarabine) is standardly used to treat relapsed Non-Hodgkin lymphoma (NHL). Despite scarce data, cisplatin is frequently substituted with oxaliplatin (R-DHAOx) to avoid nephrotoxicity. We compared nephrotoxicity of cisplatin and oxaliplatin based on creatinine-based trajectory modeling. METHODS: All patients with NHL treated by R-DHAP or R-DHAOx in Angers hospital between January 01, 2007, and December 31, 2014, were included. Patients received cisplatin 100 mg/m2 or oxaliplatin 130 mg/m2 (d1) with cytarabine (2000 mg/m2 , two doses, d2), dexamethasone (40 mg, d1-4), and rituximab (375 mg/m2 , d1). Creatinine levels were recorded before each cycle. Individual profiles of trajectories were clustered to detect homogeneous patterns of evolution. RESULTS: Twenty-two patients received R-DHAP, 35 R-DHAOx, 6 switched from R-DHAP to R-DHAOx due to nephrotoxicity. Characteristics of patients were similar between two groups. Patients receiving R-DHAP experienced more severe renal injury than patients receiving R-DHAOx (68% vs. 7.7%, P < .001). Two homogeneous clusters appeared: cluster A, with a majority of R-DHAOx (32, 91.4%), was less nephrotoxic than B, with a majority of R-DHAP (19, 86.4%), with a decreased average serum creatinine level (P < .0001). There were no other differences between clusters. CONCLUSIONS: Our study confirms that R-DHAOx regimen causes less nephrotoxicity than R-DHAP regimen.

Low-level laser therapy in treatment of chemoradiotherapy-induced mucositis in head and neck cancer: results of a randomised, triple blind, multicentre phase III trial.

BACKGROUND: Low-level laser therapy (LLLT) also called Photobiomodulation therapy (PBMT) could reduce oral mucositis (OM) incidence and severity in head and neck cancer patients treated by chemoradiotherapy, however randomised data about efficacy and safety are missing with curative dose 4 J/cm2. METHODS: This phase III trial was conducted in patients with oral cavity, or oro/hypopharyngeal cancers (stage III or IV). Patients were treated by lasertherapy on OM lesions grade ≥ 2 (4 J/cm2 or placebo), during chemoradiotherapy and until recovery. Severity of OM (incidence and duration of grades ≥3) was used as primary endpoint and blindly assessed. RESULTS: Among 97 randomised patients, 83 patients (85.6%) could be assessed finally (erroneous inclusions, chemoradiotherapy interruptions) and 32 patients had no lasertherapy because of unreachable OM lesions. Randomisation and population characteristics (sex ratio, age, chemoradiotherapy procedures, toxicities incidence) were still comparable between the two LLLT/PBMT groups. An acute OM (grade ≥ 3) was observed in 41 patients (49.4%): 23 patients (54.8%) of the active laser group versus 18 (43.9%) in the control group (modified intend to treat, p = 0.32). Median time before occurrence of OM ≥ grade 3 in half of the patients was 8 weeks in active laser group (vs. 9 weeks in control group). However, 95% of patients exhibited a very good tolerance of LLLT/PBMT. CONCLUSIONS: This study assessed LLLT/PBMT according to the Multinational Association of Supportive care in Cancer recommendations but lacked power. LLLT/PBMT was well tolerated with a good safety profile, which promotes its use in clinical routine for severe OM treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01772706 . TITLE: Laser Mucite ORL: Effectiveness of Laser Therapy for Mucositis Induced by a Radio-chemotherapy in Head and Neck Cancer (LaserMucite). Study Start Date: October 2008. Primary Completion Date: October 2016. Responsible Party: Institut de Cancérologie de l'Ouest - Paul Papin. Principal Investigator: Eric Jadaud, M.D., Institut de Cancérologie de l'Ouest - Paul Papin. FUNDING: French Ministry of Health, French national funding scheme (PHRC 2008).

Prolonged perioperative thoracic epidural analgesia may improve survival after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A comparative study.

OBJECTIVE: To assess the effectiveness of prolonged perioperative thoracic epidural analgesia (PEA) on long term survival of patients who underwent a complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases (CPM). BACKGROUND: Grade III-IV morbidity affects long term outcomes after CRS and HIPEC. As compared with opioid administered via patient-controlled analgesia (PCA), PEA reduces morbidity. METHOD: From 2005 to 2016, 150 patients underwent CRS plus HIPEC with or without prolonged PEA. Clinical data and outcomes collected from prospective database were analyzed. Survival was assessed in terms of analgesic method using Kaplan-Meier plots and a propensity score. RESULTS: Patients 'characteristics of 59 patients in PCA group were comparable to those of 91 patients in PEA group, except for age, ASA score and fluid requirements, significantly more important in PEA group. Grade III-IV morbidity was 62.7% in PCA group compared with 36.3% in PEA group (p = 0.0015). Median overall survival (OS) of PEA group was 54.7 months compared to 39.5 months in PCA group (p = 0.0078). When adjusted on the covariates, using the propensity score, the PEA significantly improves OS [HR 0.40 (95% CI: 0.28-0.56)] (p < 0.0001) and disease free survival (DFS) [HR 0.61 (95% CI: 0.45-0.81] (p < 0.0007) CONCLUSIONS: In this retrospective study of patients who underwent a complete CRS and HIPEC for colorectal peritoneal metastases, the perioperative thoracic epidural analgesia prolonged for over 72 h reduced significantly the grade III-IV morbidity and may improve OS and DFS.

Intrathecal Drug Delivery Systems for Refractory Pancreatic Cancer Pain: Observational Follow-up Study Over an 11-Year Period in a Comprehensive Cancer Center.

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer-related death in Europe and the United States. Studies have demonstrated that patients with pancreatic cancer have a high prevalence of pain, with rates varying from 47% to 82%. Analgesia using intrathecal drug delivery systems (IDDS) has been poorly studied specifically in this population. METHODS: The IDDS for pancreatic cancer pain was a follow-up observational study designed to evaluate 11-year results of IDDS for refractory pancreatic cancer pain at the Institut de Cancérologie de L'Ouest, Paul Papin in France. Patients were followed from March 2006 to April 2017. Patients were selected for IDDS based on multidisciplinary meeting discussion. All IDDS-treated patients were prescribed a combined intrathecal analgesics regimen through a catheter placed according to painful metameric level. Postimplant assessment of pain was determined using a numerical rating scale (NRS). Patients were followed via day-hospital visits and telephone calls at least monthly until death. Pain scores were compared using the Wilcoxon signed rank test. Overall survival (OS) was estimated using the Kaplan-Meier method and compared between groups by log rank tests. RESULTS: Ninety-three patients received IDDS, and total therapy duration accounts for 10,300 IDDS days. Implanted patients suffered from severe pain before implantation (median presurgical NRS, 8 [interquartile range, 7-9]) despite a median 360 mg (260-600) oral morphine equivalent daily dose. Median OS in the whole cohort after intrathecal treatment start was 82 days (95% confidence interval, 59-95). Median OS after surgery for implantable pump was 91 days (83-111) and for external pump 27 days (20-49; P < .0001). IDDS was associated with pain relief with a significant statistical difference between preimplantation NRS pain score and 1 week (median, -6 [-7 to -4]; P < .001), 1 month (median, -5 [-6 to -3]; P < .001), and 3 months (median, -6 [-7 to -4]; P < .001). Severe pain (NRS score, ≥7) decreased from 89.2% before surgery to 4.5% after 1 week, 6.7% after 1 month, and 10.3% after 3 months of IDDS implant (P < .01). Global complications rate was low, consistent with published literature. CONCLUSIONS: Despite our study's limitations, results suggest that long-term IDDS for refractory malignant pain due to pancreatic cancer was both efficacious and safe in pancreatic cancer pain. We have demonstrated, in the largest series of IDDS for pancreatic cancer pain reported yet, a clinically and statistically significant pain reduction in patients receiving IDDS.