Hypofractionated stereotactic radiotherapy for large brain metastases: Optimizing the dosimetric parameters

PurposeStereotactic radiotherapy plays a major role in the treatment of brain metastases (BM). We aimed to compare the dosimetric results of four plans for hypofractionated stereotactic radiotherapy (HFSRT) for large brain metastases.Material and methodsTen patients treated with upfront NovalisTx® non-coplanar multiple dynamic conformal arcs (DCA) HFSRT for ≥ 25 mm diameter single BM were included. Three other volumetric modulated arc therapy (VMAT) treatment plans were evaluated: with coplanar arcs (Eclipse®, Varian, VMATc_Eclipse®), with coplanar and non-coplanar arcs (VMATnc_Eclipse®), and with non-coplanar arcs (Elements Cranial SRS®, Brainlab, VMATnc_Elements®). The marginal dose prescribed for the PTV was 23.1 Gy (isodose 70%) in three fractions. The mean GTV was 27 mm³.ResultsBetter conformity indices were found with all VMAT techniques compared to DCA (1.05 vs 1.28, P < 0.05). Better gradient indices were found with VMATnc_Elements® and DCA (2.43 vs 3.02, P < 0.001). High-dose delivery in healthy brain was lower with all VMAT techniques compared to DCA (5.6 to 6.3 cc vs 9.4 cc, P < 0.001). Low-dose delivery (V5 Gy) was lower with VMATnc_Eclipse® or VMATnc_Elements® than with DCA (81 or 94 cc vs 110 cc, P = 0.02).ConclusionsNovalisTx® VMAT HFSRT for ≥ 25 mm diameter brain metastases provides the best dosimetric compromise in terms of target coverage, sparing of healthy brain tissue and low-dose delivery compared to DCA.     

Delayed diagnosis of breast cancer in women recalled for suspicious screening mammography

PurposeTo determine the frequency, pathology and causes of a delay in cancer diagnosis in women recalled for suspicious screening mammography.MethodsWe included all 290,943 screening mammograms of women aged 50–75 years, who underwent biennial screening mammography between 1st January 1995 and 1st January 2006. During a follow-up period of at least 2 years, clinical data, breast imaging reports, biopsy results and breast surgery reports were collected of all 3513 women with a positive screening result. Tumour stages of breast cancers with a diagnostic delay (defined as breast cancer confirmation more than 3 months following a positive mammography screen) were compared with those of cancers diagnosed within 3 months following referral and with interval cancers.ResultsA diagnostic delay occurred in 97 (6.5%) of 1503 screen-detected cancers. These 97 false-negative assessments comprised significantly more ductal cancers in situ (26.8%) than did cancers with an adequate assessment after recall (15.5%, p = 0.004) or interval cancers (3.7%, p < 0.001). Compared with interval cancers, cancers with a false-negative assessment had a more favourable tumour size (T1a–c, 87.3% versus T1a–c, 46.4%; p < 0.001) and showed significantly fewer cases with axillary lymph node metastases (22.5% versus 48.2%; p < 0.001). Between hospitals having performed the workup of at least 500 referred women each, the percentage of women with a false-negative assessment varied from 5.0% to 9.1% (p = 0.03). In these hospitals, improper classification of lesions at diagnostic mammography comprised 64.4% of false-negative assessments.ConclusionWe found that 6.5% of recalled women experienced a delay in breast cancer diagnosis, with significant performance variations between hospitals.     

High prevalence of deficient mismatch repair phenotype and the V600E BRAF mutation in elderly patients with colorectal cancer

AimsColorectal cancer (CRC) occurs mostly in the elderly. However, the biology of CRC in elderly has been poorly studied. This study examined the prevalence of deficient mismatch repair phenotype (dMMR) and BRAF mutations according to age.Patients and MethodsMMR phenotype was prospectively determined by molecular analysis in patients of all ages undergoing surgery for CRC. BRAF V600E mutation status was analysed in a subset of dMMR tumours.ResultsA total of 754 patients who underwent surgery between 2005 and 2008 were included in the study. Amongst them, 272 (36%) were ≥ 75 years old. The proportion of women < 75 was 38% and that ≥ 75 was 53% (p < 0.0001). The prevalence of dMMR was 19.4% in patients ≥ 75 and 10.7% in patients < 75 (p = 0.0017). For patients ≥ 75, the prevalence of dMMR was significantly higher in women than in men (27% vs 10.2%, respectively; p = 0.003) but was similar in women and men < 75 (12.5% vs 9.7%, respectively; p = 0.4). We examined BRAF mutation status in 80 patients with dMMR tumours. The V600E BRAF mutation was significantly more frequent in patients ≥ 75 than in patients < 75 (72.2% vs 11.4%, respectively; p < 0.001). In patients ≥ 75, there was no difference in the prevalence of the BRAF V600E mutation according to sex (78% in women and 70% in men, p = 0.9).ConclusionsThe prevalence of dMMR in CRC is high in patients over 75. In elderly patients, dMMR tumours are significantly more frequent in women than in men. The BRAF mutation is frequent in elderly patients with CRC.     

Small renal cell carcinomas – How dangerous are they really? Results of a large multicenter study

Aim of the studyModern diagnostic ultrasound and cross-sectional imaging has enabled the detection of increasing numbers of renal tumours. The aim of this study was to investigate the tumour- and patient-specific characteristics and prognosis of small renal cell carcinomas (RCCs) after surgical resection.MethodsThe study included 2197 patients who underwent surgical resection of histologically confirmed RCC ⩽4 cm between 1990 and 2011. Median (mean) follow-up was 56.2 (65.5) months.ResultsAt the time of surgery, tumours were staged as pT ⩾ 3a in 175 (8.0%) cases, 134 (6.2%) were poorly differentiated and 75 (3.5%) were metastasised. The larger the tumour size, the higher was the risk of presenting with stage pT ⩾ 3a (p < 0.001), poor tumour differentiation (p = 0.004), microscopic vascular involvement (p = 0.001) and collecting system invasion (p = 0.03). The 5-year cancer-specific survival (CSS) rate was 93.8% for stage pT1a versus 79.4% for stage pT ⩾ 3a (p < 0.001), and it was 93.7% for G1–2 versus 76.8% for G3–4 differentiation (p < 0.001). Multivariate analysis identified age in years (hazard ratio (HR) 1.04, p < 0.001), metastatic disease (HR 12.5, p < 0.001), tumour differentiation (HR 2.8, p < 0.001) and non-clear cell histology (HR 0.51, p = 0.02) as independent prognosticators for CSS in patients with small RCC. Interestingly, the 5-year cancer-specific mortality rate for pT1a N/M0 patients was 5.8%.ConclusionsThis large multicenter study has clearly shown that, though most small RCC have a low pathological stage and a good prognosis, there is also a small but significant subgroup of these tumours that are already locally advanced or poorly differentiated.     

Waiting times for diagnosis and treatment of head and neck cancer in Denmark in 2010 compared to 1992 and 2002

Background and aimSignificant tumour progression was observed during waiting time for treatment of head and neck cancer. To reduce waiting times, a Danish national policy of fast track accelerated clinical pathways was introduced in 2007. This study describes changes in waiting time and the potential influence of fast track by comparing waiting times in 2010 to 2002 and 1992.MethodsCharts of all new patients diagnosed with squamous cell carcinoma of the oral cavity, pharynx and larynx at the five Danish head and neck oncology centres from January to April 2010 (n = 253) were reviewed and compared to similar data from 2002 (n = 211) and 1992 (n = 168).ResultsThe median time to diagnosis was 13 days (2010) versus 17 days (2002; p < 0.001) and 20 days (1992; p < 0.001). Median days from diagnosis to treatment start were 25 (2010) versus 47 (2002; p < 0.001) and 31 (1992; p < 0.001). Total pre-treatment time was median 41 days in 2010 versus 69 days (2002) (p < 0.001) and 50 days (1992; p < 0.001). Significantly more diagnostic imaging was done in 2010 compared to 2002 and 1992. When compared to current fast track standards the adherence to diagnosis improved slightly from 47% (1992) to 51% (2002) and 64% (2010); waiting time for radiotherapy was within standards for 7%, 1% and 22% of cases, respectively; waiting time for surgery was within standards for 17%, 22% and 48%, respectively.ConclusionThe study showed a significant reduction in delay of diagnosis and treatment of head and neck cancer in 2010, but still less than half of all patients start treatment within the current standards.     

Patterns of locoregional failure in women with early-stage breast cancer treated by whole breast irradiation in the lateral isocentric decubitus position: Large-scale single-centre experience

PurposeThe purpose of this study was to evaluate locoregional control and describe the patterns of failure in patients with breast cancer receiving whole breast radiotherapy in the isocentric lateral decubitus position technique.Patients and methodsIn a series of 832 consecutive female patients with early-stage breast cancer including invasive and in situ tumours treated by breast-conserving surgery followed by three-dimensional conformal whole breast irradiation in the isocentric lateral decubitus position between 2005 and 2010, all patients who experienced locoregional recurrence were studied. Five-year recurrence-free and overall survival rates were calculated. Regional recurrence mapping patterns were also determined.ResultsThe median age of this series of 832 women was 61.5 years (range: 29–90 years). Various types of fractionation were used: 50 Gy in 25 fractions (17.9%), 66 Gy in 33 fractions (50 Gy in 25 fractions to breast followed by sequential boost to tumour bed to a total dose 66 Gy in 33 fractions.) (46.5%), 40 Gy in 15 fractions or 41.6 Gy in 13 fractions (26.1%) and 30 Gy in 5 fractions (9.5%). With a median follow-up of 6.4 years, only 36 patients experienced locoregional recurrence and no association with the fractionation regimen was identified (P = 0.2). In this population of 36 patients, 28 (3.3%) had “in-breast” local recurrences (77.8%), two had local recurrences and regional lymph node recurrence (5.6%), and six had regional lymph node recurrence only (in non-irradiated areas; 16.6%). The median time to recurrence was 50 months. Complete mapping of patterns of recurrences was performed and, in most cases, local recurrences were situated adjacent to the primary tumour bed. Cases of local recurrences presented a significantly lower distant metastasis rate (P < 0.001) and had a significantly longer overall survival compared to patients with regional lymph node recurrence (P < 0.001). However, multivariate Cox regression analysis showed that the site of recurrence had no significant impact on overall survival (P = 0.14).ConclusionThe results of this study indicate a low local recurrence rate. Further careful follow-up and recording of recurrences is needed to improve the understanding of patterns of recurrence.     

Clustering of comorbidities is related to age and sex and impacts clinical outcome in myelodysplastic syndromes

ObjectivesMyelodysplastic syndromes (MDS) are typical diseases of the elderly. The clinical outcome of a well-characterized cohort of patients with MDS was analyzed for prevalence and impact of comorbidities to establish the basis for tailored treatment algorithms. Focus was on age- and sex-related differences.Material and MethodsThe hematopoietic cell transplantation-comorbidity index (HCT-CI) was assessed in 616 well-defined patients from the Austrian MDS platform (median age: 71 years).ResultsMost patients displayed one (24.5%) or more (23.7%) comorbidities. The highest frequencies were observed for cardiovascular disease (28.4%), diabetes (12.2%), and prior tumors (9.9%). Comorbidities were more frequent (mean number: 0.92 vs. 0.74 [male vs. female]; p = 0.030) and more severe in men than in women (mean HCT-CI score: 1.41 vs. 1.09 [male vs. female]; p = 0.016). Elderly patients (65 + years) showed a higher prevalence of comorbidities than younger patients (HCT-CI score: 1.52, mean in 65 +, vs. 0.24 and 0.76 in < 45 years and 46–65 years, respectively) (p < 0.001). These differences were most pronounced for cardiovascular disease, diabetes, and prior tumors (p < 0.001). Presence of cardiac arrhythmia or prior solid tumor was significantly associated with shorter overall survival (p = 0.023, 0.024, respectively). Moreover, HCT-CI risk grouping remained an independent prognostic parameter for survival in multivariate analysis.ConclusionsComorbidities impact clinical outcome in elderly patients with MDS. Distinct diseases cluster in an age- and sex-related manner, which may have clinical implications when designing individualized therapies. Comorbidities should be evaluated with established scores and integrated in decision making.     

Predictive factors associated with complete pathological response after neoadjuvant treatment for rectal cancer

PurposeA proportion of 10 to 30% of patients treated by chemoradiotherapy followed by total mesorectal excision surgery for a locally advanced rectal cancer can achieve a complete pathological response. We aimed to identify predictive factors associated with complete pathological response or no response and to assess the impact of each response on survival rates.Patients and methodsPatients treated with long course chemoradiotherapy for locally advanced and/or node positive rectal cancer from 2010 to 2016 were retrospectively reviewed. Statistical analysis was carried out to determine predictors of tumor regression and treatment outcomes.ResultsRecords were available on 70 patients. In the univariate analysis, clinical factors associated with complete tumor response were tumor mobility in digital rectal examination (P = 0.047), a limited parietal invasion (P = 0.001), clinically negative lymph node (P < 0.001) and a circumferential extent greater than 50% (P = 0.001). On the other hand, a T4 classification and an endoscopic tumor size greater than 6 cm were associated with no response to treatment (P = 0.049 and P = 0.017 respectively). On multivariate analysis, T2 clinical classification and N0 statement before treatment were independent predictive factors of pathologic complete response (P < 0.001 and P = 0.001) and a delayed surgery after 12 weeks was associated with no response to treatment (P = 0.001).ConclusionThe identification of predictive factors of histological response may help clinicians to predict the prognosis and to propose organ preservation for good responders.     

Old age as risk indicator for poor end-of-life care quality – A population-based study of cancer deaths from the Swedish Register of Palliative Care

BackgroundIf patient age affects the quality of end-of-life care in cancer is unknown. Using data from a population-based register of palliative care in Sweden, we addressed this question.MethodsThis nation-wide study focused on the last week of life of adults dying from cancer in 2011–2012, based on data reported to a national quality register for end-of-life care (N = 26,976). We specifically investigated if age-dependent differences were present with respect to thirteen indicators of palliative care quality. Patients were categorised in one out of five pre-defined age groups. Odds ratios (OR) with 95% confidence intervals (CIs), adjusted for type of end-of-life care unit, were calculated using logistic regression, with the oldest group as reference.FindingsAge-dependent differences in implementation rate were detected for ten out of thirteen end-of-life care quality indicators, most of which were progressively less well met with each increment in age group. Compared to elderly cancer patients, young patients were more often informed about imminent death, (OR, 3.9; 95% CI 2.5–5.9, p < 0.001), were more often systematically assessed for the presence and severity of pain (OR, 1.6; 95% CI 1.2–2.1, p < 0.001) or other symptoms (OR, 1.4; 95% CI 1.0–1.9, p = 0.044), were more likely to be assessed by palliative care consultation services (OR, 4.3; 95% CI 3.3–5.7, p < 0.001) and to have injections prescribed as needed against pain (OR, 3.4; 95% CI 1.3–9.4, p = 0.016), anxiety (OR, 3.8; 95% CI 2.0–7.1, p < 0.001) or nausea (OR, 3.6; 95% CI 2.3–5.7, p < 0.001). The families of young patients were more likely to be informed about imminent death (OR, 2.6; 95% CI 1.5–4.3, p = 0.001) and to be offered bereavement support (OR, 4.6; 95% CI 2.7–7.8, p < 0.001).InterpretationOld age is a risk indicator for poor end-of-life care quality among cancer patients in Sweden.FundingThe executive committee of the National Quality Registries in Sweden.     

Health-care associated bacteremia in geriatric cancer patients with febrile neutropenia

ObjectiveThe aim of this study was to determine the epidemiology, clinical manifestations, and outcome of health-care associated bacteremia in geriatric cancer patients with febrile neutropenia.Materials and MethodsWe retrospectively evaluated cancer patients with febrile neutropenia aged ≥ 60 years with culture proven health-care associated bacteremia between January 2005 and December 2011. The date of the first positive blood culture was regarded as the date of bacteremia onset. Primary outcome was the infection related mortality, defined as the death within 14 days of bacteremia onset.ResultsThe two most common pathogens responsible for bacteremia were Staphylococcus epidermidis (36.1%) and Escherichia coli (31.5%), with high rates of methicillin resistance and extended-spectrum β-lactamase (ESBL) production, respectively. There were no statistically significant differences in infection related mortality rate according to the type of malignancy (p = 0.776). By the univariate analysis, factors associated with 14 day mortality among febrile neutropenic episodes were prolonged neutropenia (p = 0.024), persistent fever (p = 0.001), hospitalization in ICU (p < 0.001) and the initial clinical presentations including respiratory failure (p < 0.001), hepatic failure (p = 0.013), hematological failure (p < 0.001), neurological failure (p < 0.001), severe sepsis (p < 0.001), and septic shock (p = 0.036). Multivariate analysis showed that persistent fever was an independent factor associated with infection related mortality (odds ratio, 18.0; 95% confidence interval, 5.2–62.6; p < 0.001).ConclusionsThe only independent risk factor for mortality was persistent fever. Although the most frequently isolated pathogens were S. epidermidis and E. coli, high rates of methicillin resistance and ESBL production were found respectively.     

Tumor characteristics and recurrence patterns in triple negative breast cancer: A comparison between younger (<65) and elderly (⩾65) patients

BackgroundIn an aging population an increasing number of breast cancers is diagnosed in elderly women. Tumor characteristics and patterns of metastasation have been extensively elucidated in younger triple negative breast cancer (TNBC) patients, but data regarding TNBC in elderly women are missing. The goal of this investigation was to compare clinical pathological characteristics of younger and elderly TNBC patients in order to assess their relevance for TNBC in an aging population.MethodsData of TNBC patients diagnosed between 1998 and 2004 were retrospectively analyzed by computer based chart information. Baseline tumor characteristics, patient demographics and patterns of metastasation were compared between younger (<65 years) and elderly (⩾65 years) TNBC patients.ResultsOut of 254 TNBC patients 75.6% were <65 years and 24.4% were ⩾65 years. Mean tumor size, tumor grade and number of positive lymph nodes did not differ significantly (p = 0.865, 0.115 and 0.442, respectively) between both age groups. Distant visceral metastases occurred significantly more often than bone metastases in both age groups (p < 0.001). Local recurrences, bone and secondary lymph node metastases were observed at significantly higher numbers in younger patients (p = 0.035, 0.025 and 0.041, respectively). Elderly TNBC patients received significantly less chemotherapy than younger patients (p < 0.001).ConclusionsTNBC of elderly patients is an aggressive breast cancer subtype claiming as much attention as TNBC in younger patients, thus warranting chemotherapeutic intervention irrespectively of age.     

Elevated expression of HMGB1 in squamous-cell carcinoma of the head and neck and its clinical significance

PurposeHMGB1 overexpression has been reported in a variety of human cancers. However, the role of HMGB1 in squamous-cell carcinoma of the head and neck (SCCHN) remains unclear. The aim of the present investigation was to analyse HMGB1 protein expression in both SCCHN tissue and cell levels and to assess its prognostic significance in SCCHN.MethodsHMGB1 protein expression in 103 primary SCCHN tissue specimens was analysed by immunohistochemistry and correlated with clinicopathological parameters and patient outcome. Additionally, HMGB1 protein expression was evaluated in cell level by Western blotting.ResultsBy Western blotting analysis, all the 5 SCCHN cell lines overexpressed HMGB1 protein, whereas the non-transformed immortalised cell line NP-69 had relatively weak HMGB1 protein expression. Immunohistochemical staining revealed that HMGB1 protein was detected in 91 (91/103, 88.3%) primary tumour samples, but only in 7 (7/16, 43.75%) adjacent non-carcinoma samples (p < 0.001); moreover, HMGB1 overexpression was significantly associated with T classification (p = 0.001), clinical stage (p < 0.001), recurrence (p < 0.001) and lymph node metastasis (p < 0.001). Survival analysis demonstrated that high HMGB1 expression was significantly associated with shorter disease-free and overall survival (both p < 0.001), especially in late patients with SCCHN. When HMGB1 expression and lymph node status were combined, patients with HMGB1 overexpression/lymph node (+) had both poorer disease-free and overall survival than others (both p < 0.001). Multivariate analysis further demonstrated that HMGB1 was an independent prognostic factor for patients with SCCHN.ConclusionsHMGB1 protein may contribute to the malignant progression of SCCHN, and present as a novel prognostic marker and a potential therapeutic target for patients with SCCHN.     

Differences in breast cancer hormone receptor status in ethnic groups: A London population

BackgroundTriple negative breast cancer (TNBC) is associated with different ethnic groups in the United States (US), however this has not previously been examined in a population-based study within the United Kingdom (UK).MethodsElectronic pathology reports from the North East London Cancer Network (NELCN) on women diagnosed with breast cancer between 2005 and 2007 were collated. The statuses of oestrogen receptor, progesterone receptor and HER-2 were extracted. Women were classified as having TNBC if all three receptor statuses were negative, and as not having TNBC if at least one receptor was positive or borderline. Logistic regression was used to quantify the association between TNBC and ethnicity, adjusting for age, year of diagnosis and socioeconomic deprivation. Overall survival in different ethnic groups was examined using Cox regression, adjusting as appropriate for age, stage of disease, triple negative status, year of diagnosis, socioeconomic deprivation and recorded treatment.ResultsThere were 2417 women resident in NELCN diagnosed with breast cancer between 2005 and 2007, and TNBC status was determined for 1228 (51%) women. Overall, of women who had their TNBC status determined, 128 (10%) were diagnosed with TNBC. Compared with White women, Black (odds ratio [OR] = 2.81, p < 0.001) and South Asian (OR = 1.80, p = 0.044) women with breast cancer were more likely to have TNBC. Black women had a worse age-adjusted survival than White women (hazard ratio [HR] = 2.05, p < 0.001). This was attenuated by further adjustment for stage of disease (1.52, p = 0.032) and triple negative status (1.31, p = 0.175).ConclusionBetter methods of early detection may need to be developed in addition to more effective systemic treatment in order to improve outcomes for women with TNBC.     

Prognostic relevance of disseminated tumour cells from the bone marrow of early stage breast cancer patients – Results from a large single-centre analysis

BackgroundThis is the largest single-centre study to determine the prognostic relevance of disseminated tumour cells (DTCs) from the bone marrow (BM) of stage I-III breast cancer patients. Additionally, we aimed to analyse the impact of DTC detection on adjuvant bisphosphonate (BP) treatment efficacy.MethodsBM aspirates were collected during primary surgery for early breast cancer (EBC; T1–4, N0–2, M0) at Tuebingen University, Germany, between January 2001 and January 2013. DTCs were identified by immunocytochemistry (pancytokeratin antibody A45/B-B3) and cytomorphology. We retrospectively estimated the influence of DTC detection and BP treatment on disease-free survival (DFS) and overall survival (OS) using univariate (log-rank test) and multivariate (cox regression) analysis.FindingsBM aspirates were available from 3141 patients. In 803 (26%) of these, DTCs were detectable. As compared to DTC-negative patients, DTC-positive patients more frequently had larger tumors (p < 0.001), lymph node involvement (p < 0.001), hormonal receptor positive tumours (p < 0.001) and HER2-positive tumours (p = 0.048). DTC-positive patients were at an increased risk of relapse (hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.34–2.25, p < 0.001) and death (HR 1.44 95% CI 1.13–1.86, p = 0.004). In the multivariate analysis DTCs were an independent predictor of DSF and OS. Additionally, BP treatment had no significant influence on DFS or OS in DTC-negative patients, while it was significantly associated with increased DFS (p < 0.001) and OS (p = 0.006) in DTC-positive patients.InterpretationThese data confirm the clinical validity of DTCs from the BM for prognostication of early breast cancer patients. Further studies are warranted to determine whether DTCs are predictive for adjuvant treatment efficacy using bisphosphonates.     

Facteurs pronostiques et survie des cancers colorectaux métastatiques au CHU de Sousse (Tunisie) : Étude comparative de deux périodes de traitement de 200 patients

Between 1994 and 2005, 200 patients with metastatic colo-rectal cancers were treated in the Sousse CHU (Tunisia), we analysed two groups of patients, the group 1 was treated in the period after 1999 (N = 64), the group 2 was treated in the period between 1999 and 2005 (N = 136).Patients and MethodsMean age of the patients was 50 years, localisation of metastases was liver in 67.3% of cases, 23% of patients had multiple metastases, 44% of cases developed metastases after a median period of 11.4 months. All patients had received first line of chemotherapy, the regimen of chemotherapy was in the group 1, Fufol in the majority of cases (76%), the regimen of chemotherapy was in the group 2, simplified LV5FU2 associated to irinotecan in the majority of cases (83%), 28% of all patients received second line of chemotherapy.ResultsThe median survival was 13.8 months in the group 1 and 19 months in the group 2. Overall survival rates at 2 years were 35% and 42% (p = 0.02) in group 1 and 2, respectively. Prognostic factors for a better survival using univariate analysis were: normal ACE (P < 0.01), normal liver analysis (P < 0.001), response after 3 cycles of chemotherapy (P < 0.0005), resection of liver metastases (P < 0.05). The multivariate analysis (cox model) revealed only one independent factor: radiologic response after 3 cycles of chemotherapy (P < 0.03).ConclusionThe prognostic of patients with metastatic desease is poor, although palliative chemotherapy after the recent advances and the use of new drugs have been shown to be able to prolong survival and to improve the quality of life over best supportive care. This study report amelioration of prognostic and survival of metastatic colorectal cancers in Tunisia.     

Postoperative radiotherapy after flap reconstructive surgery in patients with head and neck cancer: A retrospective monocentric study with flap delineation to assess toxicity and relapse

PurposeFlaps are increasingly used during reconstructive surgery of head and neck cancers to improve functional outcomes. There are no guidelines as to whether the whole flap or its anastomotic border should be included in the primary tumour target volume of postoperative radiotherapy to prevent local relapses. Relapse and toxicity rates can increase substantially if the whole flap received full dose. Our aim was to determine whether flaps were included in the primary tumour target volume and to report the patterns of relapse and toxicity.Materials and methodsConsecutive patients in 2014 through 2016, with or without a flap, receiving postoperative radiotherapy were selected in a retrospective monocentric control study. Flaps were homogenously delineated blind to treating radiation oncologists using a flap-specific atlas. Tumour recurrence, acute and late toxicity were evaluated using univariate and propensity score analyses.ResultsA hundred patients were included; 54 with a flap. Median flap volume included in the tumour volume was 80.9%. Twelve patients experienced local recurrences: six with a flap, among whom two within their flap (3.7%). Patients with flaps had larger median tumour volumes to be irradiated (25 cm³ versus 58 cm³, p < 0.001) and higher acute/late toxicity rates (p < 0.001) even after adjustment on biases (more advanced T stage, oral cavity, active smoking in patients with flaps). Locoregional recurrence and survival rates were similar between patients with/without a flap.ConclusionRecurrences within a flap were rare in this series when including the whole flap body in the 60Gy-clinical target volume but inclusion of the flap in the primary tumour target volume increased toxicity. Multicentric studies are warranted.     

Long duration of immunotherapy before radiosurgery might improve intracranial control of melanoma brain metastases

PurposeDespite significant advances that have been made in management of metastatic melanoma with immune checkpoint therapy, optimal timing of combination immune checkpoint therapy and stereotactic radiosurgery is unknown. We have reported toxicity and efficiency outcomes of patients treated with concurrent immune checkpoint therapy and stereotactic radiosurgery.Patients and methodsFrom January 2014 to December 2016, we analyzed 62 consecutive patients presenting 296 melanoma brain metastases, treated with gamma-knife and receiving concurrent immune checkpoint therapy with anti-CTLA4 or anti-PD1 within the 12 weeks of SRS procedure. Median follow-up time was 18 months (mo) (13–22). Minimal median dose delivered was 18 gray (Gy), with a median volume per lesion of 0.219 cm³.ResultsThe 1-year control rate per irradiated lesion was 89% (CI 95%: 80.41–98.97). Twenty-seven patients (43.5%) developed distant brain metastases after a median time of 7.6 months (CI 95% 1.8–13.3) after gamma-knife. In multivariate analysis, positive predictive factors for intracranial tumor control were: delay since the initiation of immunotherapy exceeding 2 months before gamma-knife procedure (P = 0.003) and use of anti-PD1 (P = 0.006). Median overall survival (OS) was 14 months (CI 95%: 11–NR). Total irradiated tumor volume < 2.1 cm³ was a positive predictive factor for overall survival (P = 0.003). Ten patients (16.13%) had adverse events following irradiation, with four grade ≥ 3. Predictive factors of all grade toxicity were: female gender (P = 0.001) and previous treatment with MAPK (P = 0.05).ConclusionA long duration of immune checkpoint therapy before stereotactic radiosurgery might improve intracranial tumor control, but this relationship and its ideal timing need to be assessed in prospective trials.     

Internal mammary sentinel nodes: Ignore,irradiate or operate?

IntroductionThis study describes the results of internal mammary chain (IMC) biopsy, identifying factors that predict ‘hot spots’ and nodal metastases for patients in whom mapped IMC nodes were routinely dissected.MethodsThe nodal basin and status of every axillary and IMC site identified by lymphoscintigraphy were examined. Binary logistic regression analysed the relationship of several patients and tumour factors with IMC hot spots and metastases.ResultsNinety of 490 patients (18.4%) had IMC sentinel lymph nodes (SLNs) identified by lymphatic mapping and dissected, and 20 of these (22.2%) were found to have metastases. Mapping to the IMC was most likely for women aged under 35 years (29.4%) (p = 0.117), women aged 35–44 (22.6%) (p = 0.034) or those with medial (23.7%) or central tumour location (22.2%) (p = 0.014; p = 0.062, respectively). Predictors of IMC positivity included age <35 years (p = 0.063), grade 3 histology (p = 0.018) and lymphatic vascular invasion (LVI) (p = 0.032). Although IMC positivity was more likely with positive axillary nodes, this trend was not significant.ConclusionWe identified several factors (age <35 years, tumour grade and LVI) that independently predict IMC SLN identification and positivity for patients with stage I or II breast cancer. Where IMC hot spots are not dissected, we predict IMC positivity of 50% or more for young women (<35 years) or women with high grade or LVI positive tumours, and these women may benefit from more intensive chemotherapy and radiotherapy to the IMC.     

Availability of palliative care services for children with cancer in economically diverse regions of the world

PurposeWe assessed the availability and quality of palliative care for children with cancer according to national income per capita.MethodsWe surveyed physicians who care for children with cancer using the Cure4Kids website (http://www.cure4kids.org). Queries addressed oncology practice site; reimbursement; specialised palliative care, pain management and bereavement care; location of death; decision-making support and perceived quality of care. Responses were categorised by low-, middle- and high-income country (LIC, MIC and HIC).ResultsOf 262 completed questionnaires from 58 countries (response rate, 59.8%), 242 were evaluable (55%). Out-of-pocket payment for oncology (14.8%), palliative care (21.9%) and comfort care medications (24.3%) was most likely to be required in LIC (p < 0.001). Availability of specialised palliative care services, pain management, bereavement care and institutional or national decision-making support was inversely related to income level. Availability of high-potency opioids (p = 0.018) and adjuvant drugs (p = 0.006) was significantly less likely in LIC. Physicians in LIC were significantly less likely than others to report high-quality pain control (p < 0.001), non-pain symptom control (p = 0.003) and emotional support (p = 0.001); bereavement support (p = 0.035); interdisciplinary care (p < 0.001) and parental participation in decisions (p = 0.013).ConclusionSpecialised palliative care services are unavailable to children with cancer in economically diverse regions, but particularly in LIC. Access to adequate palliation is associated with national income. Programme development strategies and collaborations less dependent on a single country’s economy are suggested.     

Radionecrosis after repeated courses of radiotherapy under stereotactic conditions for brain metastases: Analysis of clinical and dosimetric data from a retrospective cohort of 184 patients

PurposeBetween 10 and 40% of patients with cancer will develop one or more brain metastases (BMs). Stereotactic radiotherapy (SRT) is part of the therapeutic arsenal for the treatment of de novo or recurrent BM. Its main interest is to delay whole brain radiation therapy (WBRT), which may cause cognitive toxicity. However, SRT is not exempt from long-term toxicity, and the most widely known SRT is radionecrosis (RN). The objective of this study was to analyze the occurrence of RN per BM and per patient.Material and methodsBetween 2010 and 2020, data from 184 patients treated for 915 BMs by two to six SRT sessions for local or distant brain recurrence without previous or intercurrent WBRT were retrospectively reviewed. RN was examined on trimestral follow-up MRI and potentially confirmed by surgery or nuclear medicine. For each BM and SRT session plan, summation V_12Gy, V_14Gy, V_21Gy and V_23Gy isodoses were collected. Volumes of intersections were created between the 12 Gy isodose at the first SRT and the 18 Gy isodose of the following SRT (V_18-12Gy).ResultsAt the end of follow-up, 23.0% of patients presented RN, and 6.3% of BM presented RN. Median follow-up of BM was 13.3 months (95%CI 18.3–20.8). The median interval between BM irradiation and RN was 8.7 months (95% CI 9.2–14.7). Six-, 12- and 24-month RN-free survival rates per BM were 75%, 54% and 29%, respectively. The median RN-free survival per patient was 15.3 months (95% CI 13.6–18.1). In multivariate analysis, the occurrence of RN per BM was statistically associated with local reirradiation (P < 0.001) and the number of SRTs (P < 0.001). In univariate analysis, the occurrence of RN per patient was statistically associated with the sum of all V_18-12Gy (P = 0.02). No statistical association was found in multivariate analysis. A sum of all V_{18-12 Gy} of less than 1.5 ml was associated with a 14.6% risk of RN, compared with 35.6% when the sum of all V_{18-12 Gy} was superior to 1.5 ml. The sum of all V_18-12Gy larger than 1.5 ml was associated with a 74% specificity and 53% sensitivity of RN (P < 0.001).ConclusionBased on these results, a small number of BMs show RN during repeated SRT for local or distant recurrent BMs. Local reirradiation was the most predictive factor of brain RN. A V_{18-12 Gy} larger than 7.6 ml in the case of local reirradiation or larger than 1.5 ml in proximity reirradiation were prognostic factors of RN. The more BM patients need radiation therapy, and the longer they survive after irradiation, the higher their individual risk of developing RN.