Worst,Average or Current Pain in the Brief Pain Inventory: Which Should be Used to Calculate the Response to Palliative Radiotherapy in Patients with Bone Metastases?

AimsTo determine which pain intensity scale in the Brief Pain Inventory correlates best with functional interference and should be used to calculate the response to palliative radiotherapy. To determine the differences in functional interference scores for patients classified as responders and non-responders to palliative radiotherapy.Patients and methodsAll patients referred to the Rapid Response Radiotherapy Program for palliative radiotherapy of symptomatic bone metastases were considered for the study. Patients rated the intensity and functional interference of their pain at the irradiated sites according to the Brief Pain Inventory before and 2 months after radiotherapy. Worst, average and current pain scores were correlated with functional interference scores using Spearman rank coefficients. Responders and non-responders to palliative radiotherapy were defined for each pain intensity scale according to the end points specified by the International Bone Metastases Consensus Working Party. Average differences between responders and non-responders were compared using a Wilcoxon rank sum test.ResultsBetween May 2003 and June 2005, 199 patients enrolled in the study (102 men and 97 women). Ninety-five patients returned complete questionnaires at 2 months of follow-up. All pain intensity and interference scores for evaluable patients were significantly lower at 2 months (P < 0.0021). Response rates differed depending on the definition of pain intensity. An overall response rate was observed in 66, 58 and 54% of patients for worst, average and current pain, respectively. Worst pain showed the best correlation with functional interference. Responders reported significantly larger decreases in functional interference scores at follow-up in general activity, normal work, enjoyment of life and average functional interference.ConclusionWorst pain intensity had higher correlations with all functional interference scores except relationships with others. Therefore, we recommend an 11-point scale measuring worst pain to evaluate response rates in future radiotherapy trials. The mean difference from baseline to follow-up in functional interference scores was significantly larger in patients who responded to radiotherapy treatment.     

Pain after Palliative Radiotherapy for Spine Metastases

AimsThe purpose of the study was to evaluate the response to palliative radiotherapy in patients with painful spinal metastatic disease (SMD).Materials and methodsThree hundred and fifty-five patients admitted to the Norwegian Radium Hospital for radiotherapy for painful SMD were included in a prospective study and were followed up 2 months later. The Brief Pain Inventory was used to assess pain. Analgesic consumption was recalculated into the daily oral morphine-equivalent dose. The radiotherapy-related response rates were calculated using the criteria of the International Bone Metastases Consensus Group (IBMCG), taking into account the use of concomitant analgesics. The response to radiotherapy was assessed as complete or partial and non-response as stable pain, pain progression or ‘other’.ResultsBrief Pain Inventory forms were obtained at follow-up from 229 of the 355 patients. Two months after radiotherapy, the median self-reported worst pain decreased significantly, but the median oral morphine-equivalent dose increased from 40 to 60 mg (P < 0.001). Forty-three per cent of the patients reported pain relief, but a radiotherapy-related response was found in 37% of the patients. Overall correspondence between the patients' self-reported changes in pain experience and the IBMCG-based response categories was obtained in 63% of the patients.ConclusionsThe radiotherapy-related response rates in our study were lower than those reported previously in patients with bone metastases in general, which possibly indicates the presence of more complex pathophysiological mechanisms of pain in SMD.     

Assessment of health-related quality of life with the European Organization for Research and Treatment of Cancer QLQ-C15-PAL after palliative radiotherapy of bone metastases

AimsTo assess health-related quality of life (HRQOL) after palliative radiotherapy for painful bone metastases using a palliative questionnaire (European Organization for Research and Treatment of Cancer QLQ-C15-PAL).Materials and methodsPatients scheduled to receive palliative radiotherapy for painful bone metastases (n = 178) completed the QLQ-C15-PAL questionnaire before treatment and at week 1, week 2, month 1 and month 2 after the first day of radiotherapy. A partial response (PR) or a complete response (CR) to radiotherapy was defined according to the International Consensus criteria. General linear regression was used to analyse changes in QOL in the entire cohort and within responders and non-responders to radiotherapy at all follow-up periods.ResultsThe overall radiotherapy response was 45% at week 1 (n = 21) (41% PR, 4% CR), 62% at week 2 (n = 28) (58% PR, 4% CR), 62% at month 1 (n = 58) (60% PR, 2% CR) and 65% at month 2 (n = 38) (60% PR, 5% CR). In general, a significant decrease in pain (P < 0.0001), insomnia (P < 0.0001) and constipation (P = 0.004) was seen by month 1 after radiotherapy. In patients who responded to radiotherapy, overall QOL significantly improved by month 2 after radiotherapy (P = 0.002). Radiotherapy responders also reported an improvement in emotional functioning together with a decrease in symptoms such as insomnia and constipation at month 1. No improvements were seen in any of the QLQ-C15-PAL scores for patients whose pain did not respond to radiotherapy.ConclusionRadiotherapy responders showed not only an improvement in pain, but also in HRQOL as assessed by QLQ-C15-PAL. As early as 1 week after radiotherapy for bone metastases, a pain relief response was reported by patients.     

Palliative radiotherapy improves pain and reduces functional interference in patients with painful bone metastases: a quality assurance study

AimsTo characterise the effect of palliative radiotherapy treatment outcomes as evaluated by the Brief Pain Inventory within a radiotherapy clinic, as a quality assurance initiative.Materials and methodsTumour and treatment parameters of patients with painful bone metastases treated through a dedicated bone pain radiotherapy clinic have been prospectively recorded since 2002. One hundred and nine ambulatory patients provided pre- and post-treatment pain assessments at 4–6 weeks after palliative radiotherapy. The self-administered Brief Pain Inventory questionnaire was completed by patients during their visits. Changes in pain and seven-item functional interference scores were analysed.ResultsMost of the patients had prostate (n = 42) or breast (n = 42) cancer. The mean Karnofsky performance score was 70 before palliative radiation therapy. Sixty-eight per cent of patients were treated with a single fraction (6–8 Gy) and 25% received 20 Gy/five fractions. The overall response (reduction in worst pain by ≥2/10) was 72%. Sixty-one per cent of patients had stable or reduced consumption of opioid analgesics. A significant reduction for all seven functional interference items was seen after treatment, the greatest improvement being general activity (−2.4/10). There was significant correlation between pain reduction and improvement in functional interference.ConclusionThis quality assurance initiative showed that palliative radiotherapy reduced both pain and its interference on function among ambulatory patients with symptomatic bone metastases. The reduction in pain was correlated with reductions in functional interference. Clinical trials of palliative radiotherapy should provide data that allow an evaluation of various domains of chronic pain.     

Sunitinib objective response in metastatic renal cell carcinoma: Analysis of 1059 patients treated on clinical trials

BackgroundRetrospective analyses were performed in patients with metastatic renal cell carcinoma (mRCC) to characterise the objective response (OR) rate to sunitinib and differentiate pretreatment features and outcomes of patients with early (response by ⩽12 weeks) versus late response, and responders versus non-responders.MethodsData were pooled from 1059 patients in six trials. Median progression-free survival (PFS) and overall survival (OS) were estimated by Brookmeyer and Crowley method and compared between groups by log-rank test. Baseline characteristics were compared by Fisher-exact, t-, or Wilcoxon rank-sum tests. Associations between characteristics and survival were investigated by Cox proportional regression analysis.Results398 patients (38%) had confirmed OR (12 complete responses); 26%, 61%, 79% and 86% responded by 6, 12, 18 and 24 weeks, respectively. Median (range) time to tumour response (TTR) was 10.6 (2.7–94.4) weeks and was similar in treatment-naïve and cytokine-refractory patients. Median response duration in early and late responders was 52.0 and 55.0 weeks, respectively. Median PFS in early versus late responders was 13.8 versus 20.2 months (P = 0.001); however, median OS did not significantly differ (37.8 versus 40.8 months; P = 0.144). Early responders had more lung metastases (P < 0.01), but baseline characteristics were otherwise mostly similar. Median PFS (16.3 versus 5.3 months) and OS (40.1 versus 14.5 months) were longer in responders versus non-responders (both P < 0.001); responders had more favourable prognostic factors.ConclusionsOR occurred in 38% of sunitinib-treated mRCC patients. Sixty-one percent of responses occurred by 12 weeks of therapy, and responders had favourable pretreatment features and significantly longer survival.     

Palliative Radiotherapy for Non-melanoma Skin Cancer

AimsThe primary objective of this study was to assess the rate of tumour response to the palliative radiotherapy regimen used at our centre (8 Gy/fraction on days 0, 7, 21) for non-melanoma skin cancer. The secondary objective was to evaluate symptom palliation.Materials and methodsA retrospective chart review identified patients treated with this palliative radiotherapy regimen from August 2003 to December 2008. Patient age, gender, tumour histology, location, size, presenting symptoms and radiation treatment factors were recorded at baseline. The tumour size and tumour-related symptoms were recorded at each fraction and follow-up visit. The results were analysed on an intent to treat basis.ResultsTwenty-eight patients received 31 courses of palliative radiation for basal cell (five) or squamous cell (26) carcinoma of the skin. Twenty-one patients with 23 tumours attended at least one follow-up visit, and seven patients had incomplete follow-up data. At the time of last follow-up (median 17 weeks), the response rate was 58.1% (complete response 15/31; partial response 3/31). A complete response to treatment was correlated with a smaller tumour size at day 21 (P = 0.0143). Presenting symptoms were alleviated in 61.3% (19/31) of symptomatic sites. No severe late toxicities were seen.ConclusionsThis palliative regimen offers impressive response rates and effective symptom palliation for patients with non-melanoma skin cancer.     

Prospective comparison of prognostic values of modified Response Evaluation Criteria in Solid Tumours with European Association for the Study of the Liver criteria in hepatocellular carcinoma following chemoembolisation

BackgroundsEuropean Association for the Study of the Liver (EASL) and modified Response Evaluation Criteria in Solid Tumours (mRECIST) guidelines, which measure changes in arterialised hepatocellular carcinoma (HCC), differ in terms of number of target lesions (all versus ?2) and calculation method (bidimensional versus unidimensional). We compared prognostic values of mRECIST for predicting overall survival (OS) with reference to EASL criteria in treatment-naïve HCC undergoing trans-arterial chemoembolisation (TACE).MethodsThe ability to predict OS during longitudinal follow-up was expressed as C-index, and a sample size of 292 patients was required to validate its equivalence between each criteria. Treatment responses were assessed using both guidelines 4 weeks after the first TACE, using dynamic computed tomography or magnetic resonance imaging. Kaplan–Meier and Cox regression analyses were used to explore differences in OS between responders (complete or partial) and non-responders (stable or progressive disease), defined by each method.ResultsC-index for EASL and mRECIST guidelines was 0.753 and 0.759, respectively, demonstrating equivalence between two methods. Differences in median OS between responders and non-responders were statistically significant for both EASL (30.1 versus 18.7 months, p < 0.001) and mRECIST (33.8 versus 17.1 months, p < 0.001) guidelines. In addition to radiological response, α-fetoprotein (p < 0.001), tumour number (p < 0.001) and tumour size (p = 0.048) were significant predictors of OS. In multivariate analysis, radiological criteria, tumour number and α-fetoprotein were identified as independent predictors (all p < 0.05).ConclusionmRECIST, a simpler method, provided prognostic values for predicting OS equivalent to EASL criteria in patients with HCC undergoing TACE as an initial treatment modality.     

Impact of early palliative care on caregivers of patients with advanced cancer: cluster randomised trial

BackgroundEarly palliative care improves the quality of life (QoL) and satisfaction with care of patients with advanced cancer, but little is known about its effect on caregivers. Here, we report outcomes of caregiver satisfaction with care and QoL from a trial of early palliative care.Patients and methodsTwenty-four medical oncology clinics were cluster-randomised, stratified by tumour site (lung, gastrointestinal, genitourinary, breast and gynaecological), to early palliative care team referral, or to standard oncology care with palliative care only as needed. Caregivers of patients with advanced cancer (clinical prognosis of 6–24 months, Eastern Cooperative Oncology Group 0–2) in both trial arms completed validated measures assessing satisfaction with care (FAMCARE-19) and QoL [SF-36v2 Health Survey; Caregiver QoL-Cancer (CQoL-C)], at baseline and monthly for 4 months. We used a multilevel linear random-intercept mixed-effect model to test whether there was improvement in the intervention group relative to the control group over 3 and 4 months.ResultsA total of 182 caregivers completed baseline measures (94 intervention, 88 control); 151 caregivers (77 intervention, 74 control) completed at least one follow-up assessment. Satisfaction with care improved in the palliative intervention group compared with controls over 3 months (P = 0.007) and 4 months (P = 0.02). There was no significant improvement in the intervention group compared with controls for CQoL-C (3 months: P = 0.92, 4 months: P = 0.51), Physical Component Summary of the SF-36v2 Health Survey (3 months: P = 0.83, 4 months: P = 0.20), or Mental Component Summary of the SF-36v2 Health Survey (3 months: P = 0.87, 4 months: P = 0.60).ConclusionEarly palliative care increased satisfaction with care in caregivers of patients with advanced cancer.ClinicalTrials.gov identifierNCT01248624.     

Progression of carotid intima media thickness after radiotherapy: A long-term prospective cohort study

Background and purposeCarotid artery vasculopathy is a long-term complication of radiotherapy (RT) of the neck. We investigated the change in carotid intima media thickness (IMT) and the incidence of ischemic stroke in the first 7 years after radiotherapy (RT) of the neck.Materials and methodsA multicentre prospective cohort study among patients treated for Head and Neck Cancer (HNC) assessed carotid IMT at baseline (before RT) and after a median of 7 years follow-up. We also screened for cerebrovascular risk factors and events.Results48 patients underwent IMT measurement at baseline and follow-up (median age 61 years, range 29–87). Mean IMT of the irradiated common carotid arteries was 0.64 mm at baseline and 0.74 mm at follow-up (p = 0.002). Mean delta IMT in the irradiated and non-irradiated common carotid arteries were 0.11 and 0.02 mm (p = 0.03). Incidence rate of stroke in our cohort, compared to the Dutch population was 8.9 versus 1.5 per 1.000 person years.ConclusionsIMT in irradiated carotid arteries was significantly increased in the first 7 years after RT. The incidence rate of stroke was six fold increased. Patients treated with RT for HNC have sustained risk for developing atherosclerosis of the carotid arteries and future stroke.     

Fiducial marker implantation in prostate radiation therapy: Complication rates and technique

PurposeThis study aims to report the complication rate from the transrectal ultrasound-guided implantation of gold seed markers in prostate radiotherapy, as well as describing the technique used.Materials and methodsBetween May 2010 and December 2012, 169 patients with localized prostate cancer had an intraprostatic fiducial marker implantation under transrectal ultrasound guidance. The procedure included prophylactic antibiotic therapy, fleet enema, implantation performed by trained radiation oncologists at our center prior to image-guided radiotherapy. Toxicity occurring between implantation and subsequent radiotherapy start date was assessed. The following parameters were analyzed via medical chart review: antibiotic therapy, anticoagulant interruption, bleeding, pain, prostate volume, number of markers implanted, post-implantation complications and delay before starting radiotherapy.ResultsOf the 169 men, 119 (70.4%) underwent insertion of 4 fiducial markers and the other 50 (29.6%) had 3. The procedure was well-tolerated. There was no interruption of the implantation with regards to pain or hemorrhage. No grade 3 or 4 complications were observed. Seed migration rate was 0.32%, for the migration of 2 markers on 626 implanted. Mean prostate volume was 38 cm³ (range: 10–150 cm³). Two patients (1.18%) developed a urinary tract infection following the procedure: prostate volume of 25 and 65 cm³, four gold seed markers implanted, urinary tract infection resistant to prophylactic antibiotherapy, and treated with antibiotics specific to their infection as determined on urine culture.ConclusionTransrectal fiducial marker implantation for image-guided radiotherapy in prostate cancer is a well-tolerated procedure without major associated complications.     

Early surgery for failure after chemoradiation in operable thoracic oesophageal cancer. Analysis of the non-randomised patients in FFCD 9102 phase III trial: Chemoradiation followed by surgery versus chemoradiation alone

BackgroundTwo randomised trials concerning thoracic oesophageal cancer concluded that for squamous cell carcinoma, chemoradiation alone leads to the same overall survival (OS) as chemoradiation followed by surgery. One of these trials, FFCD 9102, randomised only fit, compliant and operable responders to induction chemoradiation between continuation of chemoradiation and surgery. In the present analysis, the outcome in the patients not eligible for randomisation was calculated to determine if attempt of surgery should be recommended.MethodsEligible patients had operable T3-N0/N1-M0 thoracic oesophageal cancer. After initial chemoradiation, patients with no clinical response, or with contraindication to follow any attributed treatment, were not randomised. OS was studied first in the whole population of not randomised patients, and then specifically in clinical non-responders. The impact of surgery on OS was studied in these two populations.FindingsOf the 451 registered patients in the trial, 192 were not randomised. Among them, 111 were clinical non-responders. Median OS was significantly shorter for non-randomised patients (11.5 months) than for randomised patients (18.9 months; p = 0.0024). However, for the 112 non-randomised patients who underwent surgery, median OS was not different from that in randomised patients: 17.3 versus 18.9 months (p = 0.58).Concerning clinical non-responders, median OS was longer for those who underwent surgery compared to non-operated patients: 17.0 versus 5.5 months (hazard ratio (HR) = 0.39 [0.25–0.61]; p < 0.0001), and again was not different from that in responding, randomised patients (p = 0.40).InterpretationIn patients with locally advanced thoracic oesophageal cancer, overall survival did not differ between responders to induction chemoradiation and patients having surgery after clinical failure of chemoradiation. Surgery should therefore be considered in those patients who are still operable.     

Pre-treatment haemoglobin levels and the prediction of response to neoadjuvant chemotherapy in breast cancer

AimsA low pre-treatment haemoglobin level has been shown to negatively influence outcome in the treatment of tumours of the cervix, bladder and head and neck by radiotherapy. The purpose of this study was to assess the influence of baseline haemoglobin levels on the response to neoadjuvant chemotherapy for breast cancer.Materials and methodsOne hundred and thirty-nine women receiving neoadjuvant chemotherapy for operable breast tumours (T2–4, N0–1, M0) were accessed from our prospective database. Women were treated between March 1999 and June 2004. The median age was 47 years (range 25–70). Most women were treated with 5-fluorouracil, epirubicin and cyclophosphamide chemotherapy (122/139 patients). Baseline haemoglobin levels were compared for clinical responders (partial or complete) and non-responders (stable or progressive disease) using Student's t test and logistic regression. The analysis was adjusted for nodal status, tumour size, tumour grade and menopausal status.ResultsThe overall response rate was 84.9% (118/139), with a complete clinical response in 24.5% (34/139). Mean haemoglobin levels were 13.3 g/dl in responders and 13.4 g/dl in non-responders (range 7.9–15.8). The distributions of haemoglobin levels were not significantly different when comparing either responders with non-responders or ‘good’ responders with ‘poor’ responders (P = 0.70 and P = 0.32, respectively). If haemoglobin is treated as a binary variable using 12.0 g/dl as the threshold, there is a non-significant trend towards a reduction in the probability of achieving a good response if baseline haemoglobin is below 12.0 g/dl (odds ratio = 0.26, confidence interval = 0.06–1.21; P = 0.086). The rate of complete pathological response was 4.3% (6/139). The mean haemoglobin level in these patients was 14.2 g/dl (range = 12.8–15.7), but the small numbers precluded further analysis.ConclusionsThere is no evidence for an influence of pre-treatment haemoglobin levels on the clinical response to neoadjuvant chemotherapy in breast cancer. It is unlikely that correction of anaemia above that which is warranted clinically will improve outcomes.     

What to expect from immediate salvage hysterectomy following concomitant chemoradiation and image-guided adaptive brachytherapy in locally advanced cervical cancer

PurposeConcomitant chemoradiation followed by brachytherapy is the standard treatment for locally advanced cervical cancers. The place of adjuvant hysterectomy remains unclear but tends to be limited to incomplete responses to radiotherapy or local relapse. The aim was to analyse the benefit from immediate salvage surgery following radiation therapy in incomplete responders.MethodsAmong the patients with locally advanced cervical cancer treated with concomitant chemoradiation followed by 3D image-guided adaptive brachytherapy and hysterectomy, cases with genuine macroscopic remnant, defined as at least 1 cm in width, were identified. Their clinical data and outcomes were retrospectively reviewed and compared to the patients treated with the same modalities.ResultsFifty-eight patients were included, with a median follow-up of 4.2 years. After hysterectomy, 9 patients had macroscopic residual disease, 10 microscopic and the remaining 39 patients were considered in complete histological response. The 4-year overall survival and disease-free survival rates were significantly decreased in patients with macroscopic residual disease: 50 and 51% versus 92% and 93%, respectively. Intestinal grades 3–4 toxicities were reported in 10.4% and urinary grades 3–4 in 8.6% in the whole population without distinctive histological features. Planning aims were reached in only one patient with macroscopic residuum (11.1%). In univariate analysis, overall treatment time (> 55 days) and histological subtype (adenocarcinomas or adenosquamous carcinomas) appeared to be significant predictive factors for macroscopic remnant after treatment completion (P = 0.021 and P = 0.017, respectively). In multivariate analysis, treatment time was the only independent factor (P = 0.046, odds ratio = 7.0).ConclusionsAlthough immediate salvage hysterectomy in incomplete responders provided a 4-year disease-free survival of 51%, its impact on late morbidity is significant. Efforts should focus on respect of treatment time and dose escalation. Adenocarcinoma might require higher high-risk clinical target volume planning aims.     

Safety and radiation-enhancing effect of sodium glycididazole in locoregionally advanced laryngeal cancers previously treated with platinum-containing chemotherapy regimens: A preliminary report

PurposeTo determine the safety and radiation-enhancing effect of sodium glycididazole in laryngeal squamous cell carcinoma (stage T3-4,N0-3,M0) with conventional radiotherapy.Patients and methodsPatients with locoregional advanced laryngeal cancer (stage T3-4,N0-3,M0) were included: group 1(control, n = 30)were not administered of sodium glycididazole; group 2 (test, n = 30) received sodium glycididazole at a dose of 700 mg/m² intravenous infusion 30 minutes before radiotherapy three times a week. Surrogate end-points of efficacy were tumor and nodal size. Safety parameters were vomiting, nausea, mucositis, laryngeal edema, esophagus and skin reaction, dysphagia, dyspnea, neurological deficit. Patients were evaluated weekly during treatment for 7 weeks and thereafter monthly for 3 months.ResultsIn the test, the overall response rate was 88.89% (95%CI, 71.00–97.00%) at 7 weeks and 92.59% (95%CI, 76.00 to 99.00%) at 1 month of follow-up. In the control, the overall response rate was 62.5% (95%CI, 41.00 to 81.00%) at 7 weeks and 58.33% (95%CI, 37.00 to 78.00%) at 1 month of follow-up. The short-term locoregional response rate was better in the test group at 7 weeks (p = 0.027) and at 1 month (p = 0.005) of follow-up. The test group had significantly more nausea and vomiting in weeks 1 (p = 0.047), 2 (p = 0.007), and 3 (p = 0.01) of treatment.ConclusionsThe study indicates sodium glycididazole is an effective radiation-enhancing agent that improves short-term locoregional control and is well tolerated in patients with locoregionally advanced laryngeal cancer.     

Calcifications intraprostatiques : marqueurs fiduciels naturels dans la radiothérapie guidée par l’image du cancer de la prostate

PurposeTo establish whether intraprostatic calcifications can serve as natural fiducials for image-guided radiotherapy (IGRT), replacing the implantation of intraprostatic fiducial markers.Patients and methodsPatients with prostate cancer, having intraprostatic calcifications visible on CT scan were selected and underwent intensity-modulated radiotherapy/3D conformal radiotherapy with IGRT in the department of radiotherapy of Henri-Mondor Hospital. All cone-beam computed tomographies (CBCT) were repositioned on intraprostatic calcifications. For each acquired image, displacements of intraprostatic calcifications were calculated with reference to position on planning CT in three directions: lateral, longitudinal and vertical.ResultsBetween 2011 and 2013, nine patients had 183 CBCT. For each image, three displacements and space coordinates were calculated using a single reference (intraprostatic calcification). Mean lateral, longitudinal and vertical movements were 0.26 ± 5.7 mm, −1 ± 4.6 mm and 0.42 ± 3.5 mm, respectively.ConclusionStudies exploring prostatic movements with fiducial markers as reference and ours with natural fiducials yield similar results. Our data confirm previous studies that have suggested that intraprostatic calcifications can be used as natural fiducials with potential reduction of iatrogenic risks and costs associated with the implantation of fiducial markers.     

Parcours de soins en fin de vie des patients suivis en soins palliatifs à Strasbourg : étude rétrospective

ObjectivesThe goal of palliative care is to relieve suffering and provide the best possible quality of life for patients and their families. We looked for individual factors related to a poor-quality end-of-life pathway in patients followed in palliative care.MethodsWe included all the patients followed in palliative care in Strasbourg deceased from October to December of 2020. We retrospectively collected data about these patients, their first contact with palliative care, their care pathway, and their death. Multivariate analysis was undertaken.ResultsIn total, 116 patients were included. Seventy-nine of them had cancer. At the end of life, people living in an institution were less likely to be admitted to the emergency department (OR = 0.06), as were non-communicative patients (OR = 0.08). Patients expressing a wish to die at home were less likely to be admitted to and die in an intensive care unit (OR = 0.1). Isolated patients and non-communicative patients appeared protected from aggressive treatment (chemotherapy/immunotherapy, dialysis, orotracheal intubation, cardiopulmonary resuscitation) during the last month of life (OR = 0.1, OR = 0.05).DiscussionOur study suggests a profile of patients less exposed to invasive or unreasonable care at the end of life. It leads us to pay particular attention to young subjects, with family, living at home. In our population followed in palliative care, exposure to aggressive care at the end of life appeared to be very low compared to that observed in similar studies with other populations.     

Early assessment with 18F-fluorodeoxyglucose positron emission tomography/computed tomography can help predict the outcome of neoadjuvant chemotherapy in triple negative breast cancer

BackgroundIn patients with triple-negative breast cancer (TNBC), pathology complete response (pCR) to neoadjuvant chemotherapy (NAC) is associated with improved prognosis. This prospective study was designed and powered to investigate the ability of interim ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸FDG-PET/CT) to predict pathology outcomes to NAC early during treatment.Patients and methodsConsecutive TNBC women underwent ¹⁸FDG-PET/CT at baseline and after two courses of NAC. Maximum standardised uptake value (SUV_max) in the primary tumour and lymph nodes at each examination and the evolution (ΔSUV_max) between the two scans were measured. NAC was continued irrespective of PET results. Correlations between PET parameters and pathology response, and between PET parameters and event-free survival (EFS), were examined.ResultsFifty patients without distant metastases were enroled. At completion of NAC, surgery showed pCR in 19 patients, while 31 had residual tumour. Mean follow-up was 30.3 months. Thirteen patients, all with residual tumour, experienced relapse. Of all assessed clinical, biological and PET parameters, ΔSUV_max in the primary tumour was the most predictive of pathology results (p < 0.0001; Mann–Whitney-U test) and EFS (p = 0.02; log rank test). A threshold of 42% decrease in SUV was identified because it offered the best accuracy in predicting EFS. There were 32 metabolic responders (⩾42% decrease in SUV_max) and 18 non-responders. Within responders, the pCR rate was 59% and the 3-year EFS 77.5%. In non-responders, the pCR rate was 0% and the 3-year EFS 47.1%.ConclusionInterim ¹⁸FDG can early predict the inefficacy of NAC in TNBC patients. It shows promise as a potential contributory biomarker in these patients.     

Fiduciels intraprostatiques dans le cadre de la radiothérapie stéréotaxique du cancer de la prostate

PurposeImage-guided radiotherapy for prostate cancer is widely used in radiotherapy departments. Intraprostatic gold fiducial markers are used to visualize prostate position and motion before and during treatment. The aim of this report is to describe our experience of implanting intraprostatic fiducial markers under local anesthesia before hypofractionated stereotactic radiotherapy for prostate cancer and to assess its tolerance and reproducibility.Patients and methodsOver a 6 and a half year period, 226 patients with prostate cancer received a stereotactic radiotherapy using the CyberKnife^® system (Accuray) in our institution. Eighteen patients were treated for recurrence after prostatectomy; these patients were excluded from the study. Among the 208 remaining patients, 94 patients (45.2%) received stereotactic radiotherapy as a boost after external beam radiotherapy (three fractions of 6 Gy); 36 patients (17.3%) were had a re-irradiation (six fractions of 6 Gy) and 78 patients (37.5%) had a exclusive stereotactic radiotherapy (68 patients received five fractions of 7.25 Gy and 11 patients five fractions of 6.25 Gy). Four markers were implanted in all patients using transrectal ultrasound; the procedure was performed under local anesthesia, using transperineal access. The four fiducial markers were implanted in two strands with two fiducial each one, 1 cm apart. In order to follow the recommendations of the image-guided radiotherapy system, the two strands of the two markers were located on the same plane in the middle of the prostate, at least 2 cm apart from the midline. After insertion, correct positioning of fiducials markers was verified by X-ray. Dosimetry scanning was performed after the implantation procedure; prostate position tracking was possible before and during treatment through the kilovoltage incorporated system of the robotic accelerator. Clinical data, X-ray verification and dosimetry scanner have been retrospectively reviewed for all patients.ResultsThe tolerance to procedure was excellent; only four patients (1.8%) described pain related to implant. No urinary side effects were reported. Median time from fiducial implantation to dosimetry scanner was 16 days (4–113 days). Four fiducials were found within the prostate at dosimetry scanner in 181 patients and three in 27 remaining patients. All intraprostatic fiducials were used to track the prostate gland before and during treatment.ConclusionsIntraprostatic fiducial markers implantation is a safe and reproducible procedure that allows us to have reliable prostate information before and during stereotactic radiotherapy.     

Categories of response to first line vascular endothelial growth factor receptor targeted therapy and overall survival in patients with metastatic renal cell carcinoma

IntroductionSequential use of targeted therapy (TT) has improved overall survival (OS) of patients with metastatic renal cell carcinoma (mRCC). The value of objective response (OR) as compared to stable disease (SD) is unclear. We aimed to investigate OR of first-line TT and its impact on OS.Material and methodsRetrospective analysis of OS among 331 mRCC patients with a first-line assessment according to RECIST 1.0. Characteristics between objective responders (complete response [CR] or partial remission [PR]), patients with SD and non-responders (progressive disease [PD] and toxicity [Tox]) were compared with the Chi-square test and the Kruskal–Wallis test. Kaplan–Meier analysis of OS and progression-free survival (PFS). Cox model analysis of Predictors of OS .ResultsBest response was CR, PR, SD, PD and Tox in 9 (2.7%), 61 (18.4%), 167 (50.5%), 80 (24.2%) and 14 (4.2%) patients respectively resulting in an OR rate of 21%. Median OS in months: CR 63.2; PR 37.6; SD 35.9; PD 14.6; TOX 22.5 (p < 0.0001). Median PFS for responders was 14.8, 11.5 for patients with SD and 2.5 for non-responders (p < 0.0001). Similarly median OS was 38.7, 35.9 and 15.5 (p < 0.00001). Primary resistance and a first-line PFS <6 months were the strongest independent predictors of OS. The achievement of OR as compared to SD did not impact OS.ConclusionsIn our cohort of unselected patients OR was not associated with superior OS as compared to SD.     

Increased cardio and cerebrovascular mortality in breast cancer patients treated with postmastectomy radiotherapy – 25 year follow-up of a randomised trial from the South Sweden Breast Cancer Group

Aim of the studyTo analyse late morbidity and mortality in pre and post-menopausal breast cancer patients treated with postmastectomy radiotherapy, with emphasis on side-effects from the heart, cerebrovascular and respiratory systems.MethodsLong term follow-up of two randomised, clinical trials with 1100 patients was carried out. Pre-menopausal women were allocated to radiotherapy (RT), RT + oral cyclophosphamide (RT + C) or cyclophosphamide only (C). Post-menopausal women were allocated to RT, RT + Tamoxifen for one year (RT + Tam) or tamoxifen only (Tam). Information on admission to hospital, mortality and causes of death was obtained from national registers.ResultsAfter 25 years, adding RT to cyclophosphamide in pre-menopausal women raised the mortality from heart disease from zero to 0.8% (p = 0.04). In post-menopausal women, adding RT to Tam raised the mortality from heart disease from 10.5% to 18.4% (p = 0.005). In post-menopausal women mortality due to cerebrovascular disease increased from 3.4% to 8.7% by adding RT to Tam (p = 0.015). The differences were not evident until in the second decade of follow-up. In spite of differences in specific causes of death, there were no significant differences between the treatment arms concerning morbidity or overall mortality.ConclusionPostmastectomy radiotherapy to the chest wall and loco-regional lymph nodes including the parasternal lymph nodes as delivered in the end of the seventies did not reduce overall mortality, but gave a significantly increased risk of death from heart and cerebrovascular disease, which appeared during the second decade after radiotherapy.