Nomogram predicting response after chemoradiotherapy in rectal cancer using sequential PETCT imaging: A multicentric prospective study with external validation

PurposeTo develop and externally validate a predictive model for pathologic complete response (pCR) for locally advanced rectal cancer (LARC) based on clinical features and early sequential ¹⁸F-FDG PETCT imaging.Materials and methodsProspective data (i.a. THUNDER trial) were used to train (N = 112, MAASTRO Clinic) and validate (N = 78, Università Cattolica del S. Cuore) the model for pCR (ypT0N0). All patients received long-course chemoradiotherapy (CRT) and surgery. Clinical parameters were age, gender, clinical tumour (cT) stage and clinical nodal (cN) stage. PET parameters were SUV_max, SUV_mean, metabolic tumour volume (MTV) and maximal tumour diameter, for which response indices between pre-treatment and intermediate scan were calculated. Using multivariate logistic regression, three probability groups for pCR were defined.ResultsThe pCR rates were 21.4% (training) and 23.1% (validation). The selected predictive features for pCR were cT-stage, cN-stage, response index of SUV_mean and maximal tumour diameter during treatment. The models’ performances (AUC) were 0.78 (training) and 0.70 (validation). The high probability group for pCR resulted in 100% correct predictions for training and 67% for validation. The model is available on the website www.predictcancer.org.ConclusionsThe developed predictive model for pCR is accurate and externally validated. This model may assist in treatment decisions during CRT to select complete responders for a wait-and-see policy, good responders for extra RT boost and bad responders for additional chemotherapy.     

Potential utility of early metabolic response by 18F-2-fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography in a selected group of breast cancer patients receiving preoperative chemotherapy

IntroductionTo assess ¹⁸F-2-fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography’s (¹⁸F-FDG-PET/CT) potential clinical utility to allow early treatment changes during preoperative chemotherapy (PCT) in patients with early/locally advanced breast cancer (BC).Patients and methodsSixty newly diagnosed early/locally advanced BC patients received 6–8 cycles of PCT. Optimal pathologic response (pR) was the absence of cancer cells in breast and axillary lymph nodes. All other conditions were defined as pathologic non-response (pNR). ¹⁸F-FDG-PET/CT maximum standardised uptake value (SUV_max) was measured at baseline and after 2 cycles of PCT. Metabolic response was defined as SUV_max percentage changes (Δ-SUV) >50% and was compared with pR rates.ResultsThirteen (22%) patients achieved pR; according to immunohistochemistry, 16% of ER-positive/HER2-negative patients, 29% and 27% of HER2-positive and triple negative patients respectively achieved pR. ¹⁸F-FDG-PET/CT showed the highest specificity (38%) and negative predictive value (100%) in ER-positive/HER2-negative patients. In this subgroup, at a median follow-up of 36.6 months, median disease-free survival was still not reached in metabolic responders while it was 37 months in metabolic non-responders (p = 0.049).DiscussionEarly metabolic non-response was always associated to pNR and poor prognosis in ER-positive/HER2-negative patients. In this subgroup, ¹⁸F-FDG-PET/CT might be useful to select patients who will probably benefit from early therapeutic strategy modifications.     

The prognostic value of 18F-FDG PET/CT taken immediately after completion of radiotherapy for lung cancer treated with concurrent chemoradiotherapy: A pilot study

PurposeThe prognostic value of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) taken immediately after completion of radiotherapy in lung cancer patients is not well known. The purpose of this study is to assess the prognostic value of PET/CT taken immediately after completion of radiotherapy in lung cancer patients.Materials and methodsPatients with primary lung cancer planned to undergo concurrent chemoradiotherapy were enrolled. Patients underwent PET/CT scans at 3 time points: before radiotherapy, within 24 hours of completing radiotherapy (im-PET/CT), and 2–9 months after radiotherapy (post-PET/CT). Maximum standardized uptake value (SUV_max) was obtained. A post-PET/CT-SUV_max cut-off of 2.5 was determined as radiotherapy success.ResultsNineteen patients were enrolled. im-PET/CT-SUV_max for patients in the high post-PET/CT-SUV_max group was significantly higher than that of the low group (P = 0.004). Receiver operator curve analysis indicated that im-PET/CT-SUV_max of 4.35 was an optimal cut-off value to discriminate between the two groups. Multivariable analysis showed that a high im-PET/CT-SUV_max was significantly associated with a high post-PET/CT-SUV_max (P = 0.003).ConclusionPET/CT-SUV_max taken immediately following radiotherapy was associated with that evaluated 2–9 months after radiotherapy.     

Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis

BackgroundThe role of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients is highly controversial and it is not endorsed by current guidelines. Our meta-analysis aimed to better elucidate its activity, efficacy and safety.Material and methodsA systematic search of Medline, Web of Science and conferences proceedings up to 30 October 2017 was carried out to identify randomized controlled trials (RCTs) investigating platinum-based versus platinum-free neoadjuvant chemotherapy in TNBC patients. Using the fixed and random effects models, pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CI) were calculated for pathological complete response (pCR, defined as ypT0/is pN0), event-free survival (EFS), overall survival (OS) and grade 3 and 4 adverse events (AEs: neutropenia, anemia, thrombocytopenia and neuropathy).ResultsNine RCTs (N = 2109) were included. Overall, platinum-based neoadjuvant chemotherapy significantly increased pCR rate from 37.0% to 52.1% (OR 1.96, 95% CI 1.46–2.62, P < 0.001). Platinum-based neoadjuvant chemotherapy remained significantly associated with increased pCR rate also after restricting the analysis to the three RCTs (N = 611) that used the same standard regimen in both groups of weekly paclitaxel (with or without carboplatin) followed by anthracycline and cyclophosphamide (OR 2.53, 95% CI 1.37–4.66, P = 0.003). Conversely, among the 96 BRCA-mutated patients included in two RCTs, the addition of carboplatin was not associated with significantly increased pCR rate (OR 1.17, 95% CI 0.51–2.67, P = 0.711). Two RCTs (N = 748) reported survival outcomes: no significant difference in EFS (HR 0.72, 95% CI 0.49–1.06, P = 0.094) and OS (HR 0.86, 95% CI 0.46–1.63, P = 0.651) was observed.A significant higher risk of grade 3 and 4 hematological AEs, with no increased risk of grade 3 and 4 neuropathy was observed with platinum-based neoadjuvant chemotherapy.ConclusionIn TNBC patients, platinum-based neoadjuvant chemotherapy is associated with significantly increased pCR rates at the cost of worse hematological toxicities. Platinum-based neoadjuvant chemotherapy may be considered an option in TNBC patients.PROSPERO registration numberCRD42018080042.     

Prediction of local control in early glottic carcinoma using the maximum standardised uptake value

Purpose

This retrospective study aimed to determine whether the maximum standardised uptake value (SUV_max) can predict local tumour control in early glottic cancer (Tis, T1, and T2).

MRI and intraoperative pathology to predict nipple–areola complex (NAC) involvement in patients undergoing NAC-sparing mastectomy

BackgroundNipple–areola sparing mastectomy (NSM) with immediate implant reconstruction is an option for patients with non-locally advanced breast cancer. The prediction of occult tumour involvement of the nipple–areola complex (NAC) may help select candidates to NSM.Patients and methodsWe prospectively recorded clinical and pathological data, magnetic resonance imaging (MRI) results and intraoperative pathological assessments of the subareolar (SD) and proximal nipple ducts (ND) of 112 consecutive breast cancer patients scheduled for NSM. All parameters were correlated with final pathological NAC assessment by univariate and multivariate analysis.ResultsThirty-one patients (27.7%) had tumour involvement of the NAC. At univariate analysis, age (p = 0.001), post-menopausal status (0.003), tumour central location (p = 0.03), tumour–NAC distance measured by MRI (p = 0.000) and intraoperative pathologic assessment (SD + ND) (p = 0.000) were significantly correlated with NAC involvement. At multivariate analysis, only MRI tumour–NAC distance (p = 0.008) and menopausal status (p = 0.039) among all preoperative variables retained statistical significance. The sensitivity and specificity of MRI tumour–NAC distance were 32.2% and 88.6% and those of intraoperative pathologic assessment were 46.7% and 100%, respectively. Sensitivity, specificity and accuracy of the double assessment (MRI plus intraoperative pathology) were 50.0%, 96.2% and 84.1%, respectively.ConclusionIntraoperative pathologic assessment and tumour–NAC distance measured by MRI are the most important predictors of occult NAC involvement in breast cancer patients. A negative pathological assessment and a tumour–NAC distance ⩾ 5 mm allow optimal discrimination between NAC positive and NAC negative cases and may serve as a guide for the optimal planning of oncological and reconstructive surgery.     

A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study

BackgroundCombining immune-checkpoint inhibitors with chemotherapy yielded an increased response rates in patients with metastatic triple-negative breast cancer (TNBC). Therefore, we evaluated the addition of durvalumab to standard neoadjuvant chemotherapy (NACT) in primary TNBC.Patients and methodsGeparNuevo is a randomised phase II double-blind placebo-controlled study randomising patients with TNBC to durvalumab or placebo given every 4 weeks in addition to nab-paclitaxel followed by standard EC. In the window-phase durvalumab/placebo alone was given 2 weeks before start of nab-paclitaxel. Randomisation was stratified by stromal tumour-infiltrating lymphocyte (sTILs). Patients with primary cT1b-cT4a-d disease, centrally confirmed TNBC and sTILs were included. Primary objective was pathological complete response (pCR) (ypT0 ypN0).ResultsA total of 174 patients were randomised, 117 participated in the window-phase. Median age was 49.5 years (range 23–76); 47 patients (27%) were younger than 40 years; 113 (65%) had stage ≥IIA disease, 25 (14%) high sTILs, 138 of 158 (87%) were PD-L1-positive. pCR rate with durvalumab was 53.4% (95% CI 42.5% to 61.4%) versus placebo 44.2% (95% CI 33.5% to 55.3%; unadjusted continuity corrected χ²P = 0.287), corresponding to OR = 1.45 (95% CI 0.80–2.63, unadjusted Wald P = 0.224). Durvalumab effect was seen only in the window cohort (pCR 61.0% versus 41.4%, OR = 2.22, 95% CI 1.06–4.64, P = 0.035; interaction P = 0.048). In both arms, significantly increased pCR (P < 0.01) were observed with higher sTILs. There was a trend for increased pCR rates in PD-L1-positive tumours, which was significant for PD-L1-tumour cell in durvalumab (P = 0.045) and for PD-L1-immune cell in placebo arm (P = 0.040). The most common immune-related adverse events were thyroid dysfunction any grade in 47%.ConclusionsOur results suggest that the addition of durvalumab to anthracycline-/taxane-based NACT increases pCR rate particularly in patients treated with durvalumab alone before start of chemotherapy.Trial registrationClinicalTrials.gov number: NCT02685059.     

FAIRLANE,a double-blind placebo-controlled randomized phase II trial of neoadjuvant ipatasertib plus paclitaxel for early triple-negative breast cancer

BackgroundThis hypothesis-generating trial evaluated neoadjuvant ipatasertib–paclitaxel for early triple-negative breast cancer (TNBC).Patients and methodsIn this randomized phase II trial, patients with early TNBC (T ≥ 1.5 cm, N0–2) were randomized 1 : 1 to receive weekly paclitaxel 80 mg/m² with ipatasertib 400 mg or placebo (days 1–21 every 28 days) for 12 weeks before surgery. Co-primary end points were pathologic complete response (pCR) rate (ypT0/TisN0) in the intention-to-treat (ITT) and immunohistochemistry phosphatase and tensin homolog (PTEN)-low populations. Secondary end points included pCR rate in patients with PIK3CA/AKT1/PTEN-altered tumors and pre-surgery response rates by magnetic resonance imaging (MRI).ResultspCR rates with ipatasertib versus placebo were 17% versus 13%, respectively, in the ITT population (N = 151), 16% versus 13% in the immunohistochemistry PTEN-low population (N = 35), and 18% versus 12% in the PIK3CA/AKT1/PTEN-altered subgroup (N = 62). Rates of overall and complete response (CR) by MRI favored ipatasertib in all three populations (CR rate 39% versus 9% in the PIK3CA/AKT1/PTEN-altered subgroup). Ipatasertib was associated with more grade ≥3 adverse events (32% versus 16% with placebo), especially diarrhea (17% versus 1%). Higher cycle 1 day 8 (C1D8) immune score was significantly associated with better response only in placebo-treated patients. All ipatasertib-treated patients with low immune scores and a CR had PIK3CA/AKT1/PTEN-altered tumors.ConclusionsAdding ipatasertib to 12 weeks of paclitaxel for early TNBC did not clinically or statistically significantly increase pCR rate, although overall response rate by MRI was numerically higher with ipatasertib. The antitumor effect of ipatasertib was most pronounced in biomarker-selected patients. Safety was consistent with prior experience of ipatasertib–paclitaxel. A T-cell-rich environment at C1D8 had a stronger association with improved outcomes in paclitaxel-treated patients than seen for baseline tumor-infiltrating lymphocytes. This dependency may be overcome with the addition of AKT inhibition, especially in patients with PIK3CA/AKT1/PTEN-altered tumors.ClinicalTrials.govNCT02301988.     

Visualising dual downregulation of insulin-like growth factor receptor-1 and vascular endothelial growth factor-A by heat shock protein 90 inhibition effect in triple negative breast cancer

PurposeTriple negative breast cancer (TNBC) is biologically characterised by heterogeneous presence of molecular pathways underlying it. Insulin-like growth factor receptor-1 (IGF-1R) expression and vascular endothelial growth factor-A (VEGF-A) have been identified as key factors in these pathways in TNBC. In this study, we aimed at in vivo PET imaging the effect of heat shock protein (Hsp) 90 inhibition by means of NVP-AUY922 on these pathways, with zirconium-89 (⁸⁹Zr) labelled antibodies targeting IGF-1R and VEGF-A.Materials and methodsIn vitro NVP-AUY922 effects on cellular IGF-1R expression and VEGF-A secretion were determined in MCF-7 and MDA-MB-231 cell lines. Moreover human TNBC bearing MDA-MB-231 mice received 50 mg/kg NVP-AUY922 or vehicle q3d intraperitoneally for 21 days. PET scans with ⁸⁹Zr-MAB391 and ⁸⁹Zr-bevacizumab for visualisation of IGF-1R and VEGF-A were performed before and during treatment. Ex vivo biodistribution and correlative tissue analyses were performed.ResultsNVP-AUY922 treatment reduced IGF-1R expression and VEGF-A excretion in both cell lines. Hsp90 inhibition lowered tumour uptake on ⁸⁹Zr-MAB391-PET by 37.3% (P < 0.01) and on ⁸⁹Zr-bevacizumab-PET by 44.4% (P < 0.01). This was confirmed by ex vivo biodistribution with a reduction of 41.3% injected dose (ID)/g for ⁸⁹Zr-MAB391 and 37.8% ID/g for ⁸⁹Zr-bevacizumab, while no differences were observed for other tissues. This coincided with reduced IGF-1R expression and mean vessel density in the NVP-AUY922 treated tumours.Conclusion⁸⁹Zr-MAB391 and ⁸⁹Zr-bevacizumab PET reflect effect of Hsp90 inhibitors and can therefore potentially be used to monitor therapeutic effects of Hsp90 inhibitor therapy in TNBC.     

PREPARE trial: a randomized phase III trial comparing preoperative,dose-dense,dose-intensified chemotherapy with epirubicin,paclitaxel and CMF versus a standard-dosed epirubicin/cyclophosphamide followed by paclitaxel ± darbepoetin alfa in primary breast cancer—results at the time of surgery

BackgroundPreoperative chemotherapy is a recommended treatment of both primary operable and locally advanced breast cancer. Strategies to improve efficacy include the use of anthracyclines, taxanes, and intensified dose with bone marrow support.Patients and methodsPatients received neoadjuvant epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² followed by paclitaxel 175 mg/m² (EC→T), each 3-weekly for four cycles (n = 370), or epirubicin 150 mg/m² followed by paclitaxel 225 mg/m² with pegfilgrastim followed by CMF (cyclophosphamide 500 mg/m², methotrexate 40 mg/m², fluorouracil 600 mg/m²) on days 1 and 8 (E_dd→T_dd→CMF), each 2-weekly and for three cycles (n = 363). Patients were randomly allocated to either simultaneous darbepoetin alfa (DA) (n = 356) or none (n = 377).ResultsPathological complete response (pCR) rate (breast) was higher with E_dd→T_dd→CMF, 18.7% versus 13.2% with EC→T; P = 0.043, ypT0/Tis; ypN0 was reported in 20.9% versus 14.3% respectively; P = 0.019. Patients with grade 3 tumors and negative hormone receptor status had a significantly higher pCR rate. Mean hemoglobin values maintained higher with DA (13.6 versus 12.6 g/dl). E_dd→T_dd→CMF regimen showed more grade 3–4 mucositis, sensory neuropathy, and neurological complaints. Thromboembolic events were more frequent on DA (3% versus 6%; P = 0.055).ConclusionDose-dense and -intensified neoadjuvant chemotherapy with E_dd→T_dd→CMF was potentially superior to EC→T in terms of pCR. Primary use of DA did not affect pCR.     

Open-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancer

BackgroundEverolimus synergistically enhances taxane-induced cytotoxicity in breast cancer cells in vitro and in vivo in addition to demonstrating a direct antiproliferative activity. We aim to determine pharmacodynamics changes and response of adding everolimus to standard neoadjuvant chemotherapy in triple-negative breast cancer (TNBC).Patients and methodsPhase II study in patients with primary TNBC randomized to T-FEC (paclitaxel 80 mg/m² i.v. weekly for 12 weeks, followed by 5-fluorouracil 500 mg/m², epirubicin 100 mg/m², and cyclophosphamide 500 mg/m² every 3 weeks for four cycles) versus TR-FEC (paclitaxel 80 mg/m² i.v. and everolimus 30 mg PO weekly for 12 weeks, followed by FEC). Tumor samples were collected to assess molecular changes in the PI3K/AKT/mTOR pathway, at baseline, 48 h, 12 weeks, and at surgery by reverse phase protein arrays (RPPA). Clinical end points included 12-week clinical response rate (12-week RR), pathological complete response (pCR), and toxicity.ResultsSixty-two patients were registered, and 50 were randomized, 27 received T-FEC, and 23 received TR-FEC. Median age was 48 (range 31–75). There was downregulation of the mTOR pathway at 48 h in the TR-FEC arm. Twelve-week RR by ultrasound were 29.6% versus 47.8%, (P = 0.075), and pCR were 25.9% versus 30.4% (P = 0.76) for T-FEC and TR-FEC, respectively. mTOR downregulation at 48 h did not correlate with 12-week RR in the TR-FEC group (P = 0.58). Main NCI grade 3/4 toxicities included anemia, neutropenia, rash/desquamation, and vomiting in both arms. There was one case of grade 3 pneumonitis in the TR-FEC arm. No grade 3/4 stomatitis occurred.ConclusionThe addition of everolimus to paclitaxel was well tolerated. Everolimus downregulated mTOR signaling but downregulation of mTOR at 48 h did not correlate with 12-week RR in the TR-FEC group.Clinical trial numberNCT00499603.     

18-fluorodeoxy-glucose positron emission computed tomography as predictive of response after chemoradiation in oesophageal cancer patients

IntroductionThe purpose of this study was to evaluate if a baseline, an interim or a post-chemoradiation (CTRT) 18-fluorodeoxy-glucose positron emission computed tomography (18F-FDG PET/CT) studies could provide information on pathologic response to CTRT and overall survival (OS).Materials and methodsThirty-one patients with histologically proven adenocarcinoma or squamous cell carcinoma of the oesophagus, fit for trimodality therapy were prospectively enrolled. Most were men (93.5%), and had a stage III cancer (74.2%). Chemotherapy consisted of oxaliplatin/5-fluorouracil (45.2%) and taxane/5-fluorouracil (54.8%). All patients underwent a baseline, an interim (performed 12 ± 2 days after the onset of CTRT) and a post-CTRT 18F-FDG PET/CT study. The 18F-FDG PET/CT variables evaluated were at baseline, interim and post-CTRT studies maximum standardised uptake value (SUVmax) and total lesion glycolysis (TLG). Clinical and 18F-FDG PET/CT parameters were correlated with pathologic complete response (pathCR) and OS.ResultsAmong the 31 patients studied, 61.3% achieved a clinical complete response (cCR) and 87.1% had surgery. The median OS was 35.1 months (95% confidence interval (CI): 19.9–NA). PathCR rate was 22.2%. There was only a marginal association between cCR and pathCR (p = 0.06). None of the other variables was predictive of pathCR. There was association between OS and baseline TLG (p = 0.03) at the optimal cutoff TLG value of 75.15. Additionally, TLG and ΔTLG post-CTRT were also associated with OS (p = 0.01 and 0.03, respectively).ConclusionNone of the PET parameters is predictive of pathCR but TLG at baseline and post-CTRT are prognostic of OS.     

Prognostic Significance of 18F-FDG PET/CT Metabolic Parameters and Tumor Galectin-1 Expression in Patients With Surgically Resected Lung Adenocarcinoma

PurposeTo study the prognostic significance of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) metabolic parameters and tumor galectin-1 (Gal-1) expression in patients surgically treated for lung adenocarcinoma.Patients and MethodsThe medical records of 96 patients with primary lung adenocarcinoma who underwent surgery after ¹⁸F-FDG PET/CT were retrospectively reviewed. The maximal standardized uptake value (SUV_max), metabolic tumor volume, and total lesion glycolysis of the primary tumor were measured through PET/CT imaging. The expression of tumor Gal-1, glucose transporter 1 (GLUT-1), and hexokinase II (HK-II) were examined through immunohistochemistry.ResultsThere were significant positive correlations between tumor Gal-1 and SUV_max, tumor Gal-1 and metabolic tumor volume, tumor Gal-1 and total lesion glycolysis, tumor Gal-1 and GLUT-1 expression, tumor Gal-1 and HK-II expression, and SUV_max and tumor GLUT-1 and HK-II expression (P < .0001 in all cases). SUV_max was the only independent predictor of tumor Gal-1 expression. On receiver operating characteristic analysis, the optimal cutoff value of SUV_max for predicting tumor Gal-1 expression was 5.1. Progression-free and overall survival were significantly shorter in patients with Gal-1–positive tumors than in those with Gal-1–negative tumors (P ≤ .001). On multivariate analysis, advanced tumor stage (P = .001) and tumor Gal-1 expression (P < .0001) were independent prognostic indicators of poor progression-free survival, while advanced tumor stage (P < .0001) and SUV_max (P = .024) were independent prognostic indicators of poor overall survival.Conclusion¹⁸F-FDG PET/CT has the potential to be used as a noninvasive imaging modality to assess tumor Gal-1 status and prognosis in lung adenocarcinoma.     

Accelerated hyperfractionated radiotherapy within trimodality therapy concepts for stage IIIA/B non-small cell lung cancer: Markedly higher rate of pathologic complete remissions than with conventional fractionation

BackgroundRadiation dose escalation within definitive radiochemotherapy (RTx/CTx) was not successful for stage III non-small cell lung cancer (NSCLC) using conventional fractionation (CF). Accelerated-hyperfractionation (AHF) counteracts tumour cell repopulation. In this observational study, the effects of neoadjuvant RTx/CTx using AHF or CF were studied by histopathology and using the survival end-point.MethodsData from all consecutive lung cancer patients treated with neoadjuvant RTx/CTx and thoracotomy between 08/2000 and 06/2012 were analysed. Patients received induction chemotherapy (cisplatin-doublets) followed by concurrent RTx/CTx using AHF (45 Gy/1.5 Gy bid) or CF-RTx (46 Gy/2 Gy qd). For estimating the AHF versus CF treatment effects, multivariate analysis (MA), propensity score weighting (PS), and instrumental variable analysis (IV) were used.Findings239 patients were treated, median age 58 (34–78) years, stage II/IIIA/B: 19/88/132, squamous cell/adenocarcinomas/other: 98/107/34; AHF/CF-RTx 112/127 patients. No significant differences between both groups, in tumour related factors (age, gender, Charlson comorbiditiy score, lactate dehydrogenase (LDH), haemoglobin, stage, histopathology and grading), existed. Crude rates of pathologic complete responses (pCR) in AHF and CF groups were 37% and 24% respectively. The dose fractionation effect on pCR was significant (p ? 0·006, PS and IV analyses). There was a significant dependence of pCR on biologically effective dose. pCR also depended on treatment time (MA, p = 0·04; PS, p = 0·0004). Median treatment time was 22 d or 31 d using AHF or CF (p < 0.0001), respectively. Adenocarcinomas had lower pCR rates in comparison to other histologies. Five-year survival of patients with pCR was 65%, independent of the fractionation.InterpretationThis large monoinstitutional analysis demonstrates an increased effect of AHF on pCR of lung cancer which modifies overall survival.     

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.     

Predictive value of neoadjuvant chemotherapy failure in breast cancer using FDG–PET after the first course

The aim of this study was to prospectively evaluate the predictive value of ¹⁸F-fluorodeoxyglucose–positron emission tomography (FDG–PET) to detect the absence of pathological response to preoperative chemotherapy in patients (pts) with breast cancer. 63 consecutive pts with non-metastatic, non-inflammatory breast cancer, eligible for neoadjuvant chemotherapy (3 FEC 100 followed by 3 Docetaxel) were enrolled. FDG–PET was performed just before the first as well as before the second course. Metabolic activity (tumour FDG uptake) was measured by standardised uptake value (SUV_max). Pts were classified as non-responders (NR) when the decrease of SUV_max in the primary tumour was less than 15% at the time of the second PET (EORTC 1999 criteria). The metabolic response in FDG–PET was correlated with WHO criteria (clinical evaluation and ultrasound and/or mammography) evaluated after three cycles, pathological complete response (pCR) after surgery (according to Sataloff classification) and 4-year relapse-free survival (RFS). The mean SUV_max decrease according to histological response was −52 ± 21% in case of pCR (Sataloff A) and 25 ± 34% in other cases (Sataloff B + C + D). Out of the 16 pts with no PET response (SUV decrease less than 15%), only one had a clinical response after the third cycle, and no pCR was observed. The 4-year RFS rate was significantly longer for metabolic responders than for NR (respectively, 85 vs. 44%; P = 0.01). This prospective study shows that a decrease in the SUV of less than 15% after the first chemotherapy course is a very potent predictor for failure of neoadjuvant chemotherapy, especially of pCR. It is interesting to note that this was shown despite the fact that the chemotherapy regimen was changed after the third course.     

Prognostic value of 18FDG PET/CT volumetric parameters in the survival prediction of patients with pancreatic cancer

PurposeTo investigate the value of ¹⁸ FDG PET/CT volumetric parameters in the prediction of overall survival (OS) in patients with pancreatic cancer and also, assess their independence relative to well-established clinico-pathological variables.MethodsWe conducted a retrospective analysis of patients with a confirmed diagnosis of pancreatic cancer who underwent ¹⁸ FDG PET/CT. The tumour maximum standardised uptake value (SUV_max) in addition to SUV_mean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated. The prognostic value of ¹⁸ FDG PET/CT and clinico-pathological parameters for OS were assessed using univariate and multivariable analyses.ResultsA sum of 89 patients were analysed in this study. Median survival for patients categorised as having high TLG (≥55) and low TLG (<55) was 18 vs 5 months (p < 0.001). Similarly, the respective high vs low SUV_mean, MTV and SUVmax were 18 vs 6 months (p = 0.001), 16 vs 6 months (p = 0.002) and 18 vs 6 months (p = 0.001). Univariate analysis showed SUV_max, SUV_mean, MTV, TLG, tumour size, tumour differentiation and presence of distant metastasis as prognostic factors for OS. On multivariable analysis, TLG (HR 2.0, 95% CI 1.26–3.18, p = 0.004) and the presence of distant metastasis (HR 3.37, 95% CI 1.97–5.77, p < 0.001) emerged as independent prognostic factors. Subgroup analysis identified TLG as the only significant PET metric after adjusting for the presence of distant metastasis.Conclusions¹⁸ FDG PET/CT is a useful tool in the preoperative evaluation of patients with pancreatic cancer. Tumour TLG offer an independent prognostic value in both potentially operable and metastatic disease settings.     

Treatment of adult nonmetastatic medulloblastoma patients according to the paediatric HIT 2000 protocol: A prospective observational multicentre study

BackgroundMedulloblastoma in adulthood is rare. Knowledge is limited, and the efficacy and toxicity of chemotherapy – especially in nonmetastatic disease – is still elusive.MethodsSeventy adults aged ?21 years (median age: 28.5 years) with nonmetastatic medulloblastoma were followed as observational patients within the prospective paediatric multicentre trial HIT 2000. Treatment consisted of radiotherapy (35.2 Gy to the craniospinal axis and a boost to 55.2 Gy to the posterior fossa) followed in most patients by maintenance chemotherapy (lomustine (CCNU), vincristine and cisplatin, n = 49).ResultsThe implementation of maintenance chemotherapy was feasible. Peripheral neuropathy (74%) and haematotoxicity (55%) during maintenance chemotherapy appear to be more common in adults than in children. At a median follow-up of 3.7 years, the 4-year event-free survival (EFS) and overall survival (OS) rates ± standard error (SE) were 68% ± 7% and 89% ± 5%. Patients with desmoplastic medulloblastoma and lateral tumour location (n = 19) had a lower EFS compared to patients with centrally located desmoplastic tumours (n = 10) (p = 0.011). Absence of residual postoperative tumour (n = 40) was associated to a lower rate of progression/relapse compared to present (n = 11) or unknown (n = 12) residual tumour status (p = 0.006). Lateral tumour location and unknown residual tumour status were independent negative prognostic factors.ConclusionsMaintenance chemotherapy is applicable in adults with nonmetastatic medulloblastoma. Histological subtype and tumour location were newly identified risk factors in this age-group, and should be further analysed in prospective trials.