Different outcomes for relapsed versus refractory neuroblastoma after therapy with 131I-metaiodobenzylguanidine (131I-MIBG)

Background¹³¹I-metaiodobenzylguanidine (¹³¹I-MIBG) is a targeted radiopharmaceutical with significant activity in high-risk relapsed and chemotherapy-refractory neuroblastoma. Our primary aim was to determine if there are differences in response rates to ¹³¹I-MIBG between patients with relapsed and treatment-refractory neuroblastoma.MethodsThis was a retrospective cohort analysis of 218 patients with refractory or relapsed neuroblastoma treated with ¹³¹I-MIBG at UCSF between 1996 and 2014. Results were obtained by chart review and database abstraction. Baseline characteristics and response rates between relapsed patients and refractory patients were compared using Fisher exact and Wilcoxon rank sum tests, and differences in overall survival (OS) were compared using the log-rank test.ResultsThe response rate (complete and partial response) to ¹³¹I-MIBG-based therapies for all patients was 27%. There was no difference in response rates between relapsed and refractory patients. However, after ¹³¹I-MIBG, 24% of relapsed patients had progressive disease compared to only 9% of refractory patients, and 39% of relapsed patients had stable disease compared to 59% of refractory patients (p = 0.02). Among all patients, the 24-month OS was 47.0% (95% confidence interval (CI) 39.9–53.9%). The 24-month OS for refractory patients was significantly higher at 65.3% (95% CI 51.8–75.9%), compared to 38.7% (95% CI 30.4–46.8%) for relapsed patients (p < 0.001).ConclusionsAlthough there was no significant difference in overall response rates to ¹³¹I-MIBG between patients with relapsed versusrefractory neuroblastoma, patients with prior relapse had higher rates of progressive disease and had lower 2-year overall survival after ¹³¹I-MIBG compared to patients with refractory disease.     

Long-term risk of subsequent cancer incidence among hereditary and nonhereditary retinoblastoma survivors

Background Increased sarcoma and melanoma risks after hereditary retinoblastoma are well established, whereas less is known about epithelial subsequent malignant neoplasms (SMNs) and risks for multiple (≥2) SMNs.Methods Leveraging long-term follow-up and detailed histologic information, we quantified incident SMN risk among 1128 hereditary and 924 nonhereditary retinoblastoma survivors (diagnosed 1914–2006; follow-up through 2016). Standardised incidence ratios (SIRs) compared cancer risk after retinoblastoma relative to the general population. We estimated cumulative incidence accounting for competing risk of death.Results Hereditary survivors had statistically significantly increased SMN risk (N = 239; SIR = 11.9; 95% confidence interval [CI] 10.4–13.5), with SIRs >80-fold for sarcomas, nasal cavity tumours and pineoblastoma. Significantly increased risks were also observed for melanoma and central nervous system, oral cavity and breast SMNs (SIRs = 3.1–17), but not the uterus, kidney, lung, bladder, pancreas or other types. Cumulative incidence 50 years following hereditary retinoblastoma was 33.1% (95% CI 29.0–37.2) for a first SMN and 6.0% (95% CI 3.8–8.2) for a second SMN. SMN risk was not increased after nonhereditary retinoblastoma (N = 25; SIR = 0.8; 95% CI 0.5–1.2).Conclusion Beyond the established sarcoma and melanoma risks after hereditary retinoblastoma, we demonstrate increased risk for a more limited number of epithelial malignancies than previously suggested. Cumulative incidence estimates emphasise long-term SMN burden after hereditary retinoblastoma.Subject terms: Cancer epidemiology, Eye cancer, Paediatric cancer     

Synergistic effect of clinicopathological factors on mortality risk in patients with differentiated thyroid cancer: An analysis using the SEER database

ObjectivesIn this study, we analyzed the effects of histology subtypes, lymph node N-stages, and the presence of extrathyroidal extensions on cancer-specific survival (CSS) and overall survival (OS) in patients with differentiated thyroid cancer.Materials and methodsCox proportional hazards regression analyses were carried out to evaluate the correlations between clinicopathological factors and CSS/OS. The combined effects of these factors on CSS and OS were then analyzed to determine the relative excess risk, attributable proportion, and synergy index. Kaplan-Meier curves were used to evaluate the mortality rate.ResultsA total of 86033 cases were included in the analysis. Histology subtype, N-stage, and extrathyroidal extension were all found to be risk factors for CSS (hazard ratio [HR] = 1.8, 95% confidence intervals [CI]: 1.4–2.3, p < 0.001; HR = 1.9, 95% CI: 1.6–2.3, p < 0.001; HR = 1.4, 95% CI: 1.0–1.9, p = 0.035, respectively). The risk factors for OS were histology subtype and N-stage (HR = 1.3, 95% CI; 1.2–1.5, p < 0.001; HR = 1. 4, 95% CI: 1.3–1.5, p < 0.001, respectively) but not extrathyroidal extension (HR = 1.1, 95% CI: 0.9–1.3, p = 0.228). Furthermore, histology subtype and N-stage, histology subtype and extrathyroidal extension, and N stage and extrathyroidal extension (relative excess risk, attributable proportion, and synergy index: 48.8, 0.9, 7.6; 50.2, 0.7, 3.9; 7.0, 0.3, 1.6; respectively) were found to have significant synergistic effects.ConclusionPatients with follicular thyroid carcinoma (FTC) and extrathyroidal extension or lymph node metastasis are at a higher risk of mortality. Histology subtype, N-stage, and extrathyroidal extension appear to have synergistic effects on the increased risk of poor CSS in patients. This result can in the further development of treatment guidelines to improve the outcome of FTC patients.     

Second malignancies in children with neuroblastoma after combined treatment with 131I-metaiodobenzylguanidine

BACKGROUND: (131)I-metaiodobenzylguanidine ((131)I-MIBG) is selectively taken up by cells of neural crest origin, allowing targeted radiotherapy of tumors such as neuroblastoma (NB) and pheochromocytoma. Radiotherapy may provide additional benefits in the treatment of NB, with moderate side effects such as hematologic and thyroid toxicity. However, with longer follow-up, other complications might occur. We describe our experience with second cancers occurring in children treated with (131)I-MIBG and chemotherapy. METHODS: The clinical records of 119 consecutive NB cases treated with (131)I-MIBG at a single institution between 1984 and 2001 were reviewed for the occurrence of a second malignant neoplasm (SMN). RESULTS: Overall, five cases of SMN occurred in the study patients. In particular, two cases of myeloid leukemia, one of angiomatous fibrous histiocytoma, one of malignant schwannoma, and one case of rhabdomyosarcoma were detected. The schwannoma and the rhabdomyosarcoma developed within the residual neuroblastic mass after first-line therapy. CONCLUSIONS: Should (131)I-MIBG treatment become more broadly employed in the therapeutic strategy for neuroblastoma, the risk of second cancer will have to be taken into consideration. The organization of an international registry of subjects treated with (131)I-MIBG might better define the frequency and features of second malignancies following this radiometabolic approach.     

Incidence of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) including CNS relapse in a population-based cohort of 4243 patients in Sweden

We performed a national population-based study of all patients diagnosed with diffuse large B-cell lymphoma (DLBCL) in Sweden in 2007–2014 to assess treatment intent and risk of relapsed/refractory disease, including central nervous system (CNS) relapse, in the presence of competing risks. Overall, 84% of patients started treatment with curative intent (anthracycline-based) (n = 3550, median age 69 years), whereas 14% did not (n = 594, median age 84 years) (for 2% the intent was uncertain). Patients treated with curative intent had a 5-year OS of 65.3% (95% CI: 63.7–66.9). The median OS among non-curatively treated patients was 2.9 months. The 5-year cumulative incidence of relapsed/refractory disease in curative patients was 23.1% (95% CI: 21.7–24.6, n = 847). The 2-year cumulative incidence of CNS relapse was 3.0% (95% CI: 2.5–3.6, n = 118) overall, and 8.0% (95% CI: 6.0–10.6, n = 48) among patients with high CNS-IPI (4–6), when considering other relapse locations and death as competing events. The incidence of relapsed/refractory DLBCL overall and in the CNS was lower than in previous reports, still one in seven patients was not considered fit enough to start standard immunochemotherapy at diagnosis. These results are important for quantification of groups of DLBCL patients with poor prognosis requiring completely different types of interventions.Subject terms: Epidemiology, Cancer epidemiology, B-cell lymphoma     

Second primary colorectal cancers (SPCRCs): experiences from a large Australian Cancer Registry

BackgroundWe examined the rate of second primary colorectal cancer (SPCRC) in a cohort of 29 471 patients first diagnosed with colorectal cancer (CRC) from 1987 to 1996, in New South Wales (NSW), Australia.MethodsThe 5-year age group, date and site of first and subsequent CRC diagnoses as well as death dates were obtained from the NSW Central Cancer Registry. The time to SPCRC and standardised incidence ratios (SIRs) were generated.ResultsSix hundred and sixty patients (2.1%) developed SPCRCs and the cumulative incidence at 18 years was 5.5%, 95% confidence interval (CI) 4.9% to 6.3%. The risk of SPCRC was increased in patients with a CRC history compared with the general population (SIR = 1.5, 95% CI 1.4–1.6) and inversely related to age at first diagnosis (30–49 years, SIR = 5.1, 95% CI 3.6–7.1 versus ≥80 years, SIR = 1.1, 95% CI 0.9–1.4). The excess absolute risk of SPCRC was greater for females aged 50–69 years at first diagnosis than for males in the same age group. SPCRC was also increased in individuals with right-sided first primaries (SIR = 2.0, 95% CI 1.6–2.4).ConclusionsThe SPCRC rate was increased during the first 5 years after first diagnosis but remained increased for up to 10 years in females, in patients with right-sided cancers and in patients <60 years at first diagnosis. These findings support active surveillance up to 10 years in these risk groups.     

Spinal lesions in multiple myeloma: Primary bone tumors with distinct prognostic factors

PurposeAlthough prognostic factors of spinal multiple myeloma (MM) seem to differ from those of other spine metastases (SpM), the data in the literature remains scarce.MethodsA prospective population of 361 patients treated for spine MM lesions between January 2014 and 2017.ResultsOS for our series was 59.6 months (SD 6.0 months; CI 95%: 47.7–71.3). Cox multivariate proportional-hazards analysis showed that bone marrow transplant [HR: 0.390, 95% CI 0.264–0.577; p < 0.0001] and light-chain isotype [HR: 0.748, 95% CI 0.318–1.759; p = 0.005] were independent predictors of longer survival. In contrast, age >80 years [HR: 2.7, 95% CI 1.6–4.3; p < 0.0001], ISS III [HR: 2.510, 95% CI 2.01–3.124; p = 0.001], IgA isotype [HR: 1.475, 95% CI 1.031–2.11; p = 0.034] and IgD/M isotype [HR: 2.753, 95% CI 1.230–6.130; p = 0.013] were independent poor prognostic factors. However, ECOG (p = 0.486), spine surgery (p = 0.391), spine radiotherapy (p = 0.260), epidural involvement (p = 0.259), the number of vertebra lesions (p = 0.222), and synchronous/metachronous timeline (p = 0.412) were not significantly associated with improved OS.ConclusionsSpinal involvement in the context of MM does not influence OS. The main prognostic factors to consider before spinal surgery are the characteristics of the primary MM disease (ISS score, IgG isotype and systemic treatment).     

Iodine-131-metaiodobenzylguanidine as initial induction therapy in stage 4 neuroblastoma patients over 1 year of age

PurposeTo determine the response to radionuclide targeted therapy with I-131-metaiodobenzylguanidine (¹³¹I-MIBG) as induction therapy in high-risk neuroblastoma patients.Patients and methodsThe protocol dictated at least two cycles of ¹³¹I-MIBG with a fixed dose of 7.4 and 3.7 GBq, respectively, followed by surgery, if feasible, or followed by neoadjuvant chemotherapy and surgery. This was followed by consolidation with four courses of chemotherapy myeloablative chemotherapy and autologous stem-cell transplantation (ASCT). Consolidation therapy with 13-cis-retinoic acid was given for 6 months.ResultsOf 44 consecutive patients, 41 were evaluable after two courses of ¹³¹I-MIBG. The objective response rate at this point was 66%. In 24 patients, ¹³¹I-MIBG was continued as pre-operative induction treatment. Seventeen patients required additional chemotherapy before surgery. After pre-operative therapy and surgery, the overall response rate was 73%.ConclusionFirst line ¹³¹I-MIBG-targeted therapy is a valuable tool in the treatment of MIBG-positive high-risk neuroblastoma patients.     

Long-term results of gemcitabine plus oxaliplatin with and without rituximab as salvage treatment for transplant-ineligible patients with refractory/relapsing B-cell lymphoma

Purpose  To determine the efficacy and safety of the combination of gemcitabine plus oxaliplatin, with and without rituximab, in patients with relapsed/refractory B-cell lymphoma unsuitable for high dose therapy. Methods  Patients were prospectively enrolled in two subsequent trials, GEMOX [gemcitabine (1200 mg/m², days 1 and 8) and oxaliplatin (120 mg/m², day 2), three-weekly] and R-GEMOX [rituximab (375 mg/m², day 1), gemcitabine (1200 mg/m², day 1) and oxaliplatin (120 mg/m², day 2), bi-weekly], up to six courses. Results  Sixty-two patients were enrolled: GEMOX [n = 30; median age, 66 years (range, 46–85); previous chemotherapy ≥2, 70%; PS ECOG ≥ 2, 57%]; R-GEMOX [n = 32; median age, 65 years (range 32–79); previous chemotherapy ≥2, 75%; PS ECOG ≥ 2, 47%]. Overall and complete response rates were 57 and 30% (95% CI, 15–49) for GEMOX and 78 and 50% (95% CI, 32–68) in R-GEMOX, respectively. Grade 3/4 neutropenia occurred in 57 and 47% of cycles and grade 3/4 thrombocytopenia in 26 and 17% of courses for GEMOX and R-GEMOX, respectively. At 42 months, the failure-free survival (FFS) was 7% (95% CI, 0–16) for GEMOX and 28% (95% CI, 9–47) for R-GEMOX (P = 0.014), with overall survivals of 7 (95% CI, 0–16) and 37% (95% CI, 20–55), respectively (P = 0.016). Conclusions  Both regimes showed good tolerability and appealing response rates. FFS was more prolonged in R-GEMOX, but patients continuously relapsed without a clear plateau on survival curves.     

High-risk factors for lymph node metastasis in contralateral central compartment in unilateral papillary thyroid carcinoma（cT1N0）

ObjectiveThe incidence of papillary thyroid carcinoma (PTC) increases yearly. Central lymph node metastasis (CLNM) is common in PTC. Many studies have addressed ipsilateral CLNM; however, few studies have evaluated contralateral CLNM. The purpose of this study is to investigate the high-risk factors of lymph node metastasis in the contralateral central compartment of cT1 stage in PTC.MethodsIn total, 369 unilateral PTC (cT1N0) patients who underwent total-thyroidectomy with bilateral central lymph node dissection (CLND) between 2013 and 2016 in our hospital were retrospectively enrolled. Univariate and multivariate analyses identified the high-risk factors for contralateral CLNM of PTC.ResultsThe total metastasis rate of the ipsilateral central neck compartment was 31.71% (117/369). The total metastasis rate of the contralateral central neck compartment was 8.13% (30/369). The multivariate analysis showed that multifocality (p = 0.009), ipsilateral CLNM (p＜0.001), number of ipsilateral CLNM ＞2 (p = 0.006), tumor located at the inferior pole (p = 0.032) and tumor diameter ＞ 1 cm (p = 0.029) were independent risk factors for contralateral CLNM at cT1 stage in PTC, with odds ratios (ORs) of,4.132 (95% confidence intervals (CI): 1.430–11.936) ，8.591 (95% CI: 3.200–23.061) ，0.174 (95% CI: 0.050–0.601) ，0.353 (95% CI: 0.136–0.917)and 0.235 (95% CI: 0.064–0863), respectively.ConclusionThe combinational use of these risk factors will help surgeons devise an appropriate surgical plan preoperatively. This information could provide reference for the readers who are interested and help to determine the optimal extent of CLND in patients with PTC, especially for cT1b patients.     

Planned combined onco-plastic (COP) surgical approach improves oncologic outcomes in soft tissue sarcomas

BackgroundCombined modality of radiotherapy and surgery is the standard of treatment of soft tissue sarcomas (STS). The goal of this study was to assess whether a Combined Onco-Plastic (COP) surgical approach in the setting of neo-adjuvant radiotherapy can improve the oncologic outcomes of STS and reduce the rate of wound complications.MethodsWe performed a retrospective review of all patients with STS treated at a single sarcoma centre (St Vincent’s Hospital, Melbourne) between 2007 and 2018. Patients were stratified into two groups based on whether they have received the COP approach or were closed primarily by the orthopaedic surgeon. We analysed oncological outcomes and rate of wound complications.ResultsA total of 546 patients with comparable demographics and tumor characteristics were included. The COP approach was performed in 75.6% of the patients. Wide margins were obtained in 97.4% of the cases, and this was significantly higher in the COP group (p < 0.001). The cumulative rate of local recurrence was 4.9%, with a 52% risk reduction in the COP approach, although this reduction was not significant (HR = 0.48; 95% CI 0.21–1.06; p = 0.070). The COP approach had better disease free survival (DFS) (aHR 1.86, 95% CI 1.45–2.37; p < 0.001) and Overall survival (risk of death aHR 0.49; 95% CI 0.30–0.79; p = 0.004). The overall wound complication rate was 18.6% with no difference between the two groups.ConclusionA planned collaboration between the orthopaedic oncologist and the plastic surgeon is beneficial in the treatment of STS after neo-adjuvant radiotherapy, allowing remarkably good oncological outcomes and a low rate of wound complications.     

Survival in breast cancer patients with spine metastases: Prognostic assessment involving molecular markers

BackgroundTo clarify and update the prognostic assessment for heterogeneous population of patients with breast cancer and spine metastases (SpM), using molecular markers.MethodsThe patient data used in this study was obtained from a French national multi-center database of patients treated for breast cancer with SpM between 2014 and 2017. 556 SpM cases were diagnosed.ResultsMedian overall survival (OS) time for all patients following the SpM event was 43.9 months. First, we confirmed 3 previously known significant prognostic factors for survival of patients with SpM: young age [HR: 2.019, 95% CI 1.343–3.037; p = 0.001], good WHO status [ Status 0 HR: 2.823, 95% CI 1.231–3.345; p < 0.0001] or [ Status 1 HR: 1.956, 95% CI 0.768–2.874; p = 0.001] and no-ambulatory neurological status: Frankel A-C [HR: 0.438, 95% CI 0.248–0.772; p = 0.004]. Secondly, we determined the effect of gene mutations on survival in patients with SpM, and we identified that HER2+ cancer subtype [HR: 1.567, 95% CI 0.946–2.557; p = 0.008] was an independent predictor of longer survival, whereas basal cancer subtype [HR: 0.496, 95% CI 0.353–0.699; p < 0.0001] was associated with a poorer prognosis. Other factors including the number of SpM, surgery, extraspinal metastases, synchrone metastases, metastasis-free survival, and SpM recurrence were not identified as prognostically relevant to survival.ConclusionSurvival and our ability to estimate it in breast cancer patients with SpM has improved significantly. Therefore, SpM prognostic scoring algorithms should be updated and incorporate genotypic data on subtypes to make treatment more adaptive.     

Risk factors for local recurrence and long term survival after minimally invasive intersphincteric resection for very low rectal cancer: Multivariate analysis in 161 patients

IntroductionIntersphincteric resection (ISR) is the ultimate anal-sparing technique as an alternative to abdominoperineal resection in selected patients. Oncological safety is still debated. This study analyses long-term oncological results and evaluates risk factors for local recurrence (LR) and overall survival (OS) after minimally-invasive ISR.Materials and methodsRetrospective single-center data were collected from a prospectively maintained colorectal database. A total of 161 patients underwent ISR between 2008 and 2018. OS and local recurrence-free survival (LRFS) were assessed using Kaplan-Meier analysis (log-rank test). Risk factors for OS and LRFS were assessed with Cox-regression analysis.ResultsMedian follow-up was 55 months. LR occurred in 18 patients. OS and LRFS rates at 1, 3, and 5 years were 96%, 91%, and 80% and 96%, 89%, and 87%, respectively. Tumor size (p = 0.035) and clinical T-stage (p = 0.029) were risk factors for LRFS on univariate analysis. On multivariate analysis, tumor size (HR 2.546 (95% CI: 0.976–6.637); p = 0.056) and clinical T-stage (HR 3.296 (95% CI: 0.941–11.549); p = 0.062) were not significant. Preoperative CEA (p < 0.001), pathological T-stage (p = 0.033), pathological N-stage (p = 0.016) and adjuvant treatment (p = 0.008) were prognostic factors for OS on univariate analysis. Preoperative CEA (HR 4.453 (95% CI: 2.015–9.838); p < 0.001) was a prognostic factor on multivariate analysis.ConclusionsThis study confirms the oncological safety of minimally-invasive ISR for locally advanced low-lying rectal tumors when performed in experienced centers. Despite not a risk factor for LR, tumor size and, locally advanced T-stage with anterior involvement should be carefully evaluated for optimal surgical strategy. Preoperative CEA is a prognostic factor for OS.     

High-dose chemotherapy and autologous hematopoietic progenitor cell transplantation for non-Hodgkin's lymphoma in patients >65 years of age

Patients and methodsWe present a retrospective analysis of 99 consecutive patients with relapsed non-Hodgkin's lymphomas who were older than 65 years at the time of high-dose chemotherapy and autologous progenitor cell transplantation.ResultsMedian age at transplant was 68 years (range 65–82). Thirty-six percent of patients had a hematopoietic cell transplantation comorbidity index of >2 at the time of transplantation. The cumulative nonrelapse mortality was 8% [95% confidence interval (CI) 4–17] at 26 months and the 3-year overall survival (OS) was 61% (95% CI 49–71). On multivariate analysis, disease status at transplant and lactate dehydrogenase (LDH) > normal were significant predictors for OS (P = 0.002). Comorbidity index of >2 did not impact OS but did predict for higher risk of developing grade 3–5 toxicity (P = 0.006). Eight patients developed secondary myelodysplastic syndrome/acute myelogenous leukemia after transplantation (cumulative incidence 16%).ConclusionsPatients with relapsed lymphomas who are >65 years of age should be considered transplant candidates, particularly if they have chemosensitive disease and normal LDH levels at the time of transplantation. Patients with comorbidity index of >2 can also undergo transplantation with acceptable outcomes but may be at higher risk for developing toxicity.     

Hematologic toxicity of high-dose iodine-131-metaiodobenzylguanidine therapy for advanced neuroblastoma.

PURPOSE: Iodine-131-metaiodobenzylguanidine ((131)I-MIBG) has been shown to be active against refractory neuroblastoma. The primary toxicity of (131)I-MIBG is myelosuppression, which might necessitate autologous hematopoietic stem-cell transplantation (AHSCT). The goal of this study was to determine risk factors for myelosuppression and the need for AHSCT after (131)I-MIBG treatment. PATIENTS AND METHODS: Fifty-three patients with refractory or relapsed neuroblastoma were treated with 18 mCi/kg (131)I-MIBG on a phase I/II protocol. The median whole-body radiation dose was 2.92 Gy. RESULTS: Almost all patients required at least one platelet (96%) or red cell (91%) transfusion and most patients (79%) developed neutropenia (< 0.5 x 10(3)/microL). Patients reached platelet nadir earlier than neutrophil nadir (P <.0001). Earlier platelet nadir correlated with bone marrow tumor, more extensive bone involvement, higher whole-body radiation dose, and longer time from diagnosis to (131)I-MIBG therapy (P 相似文献   

Gemcitabine–erlotinib versus gemcitabine–erlotinib–capecitabine in the first-line treatment of patients with metastatic pancreatic cancer: Efficacy and safety results of a phase IIb randomised study from the Spanish TTD Collaborative Group

BackgroundGemcitabine and erlotinib have shown a survival benefit in the first-line setting in metastatic pancreatic cancer (mPC). The aim of this study was to assess whether combining capecitabine (C) with gemcitabine + erlotinib (GE) was safe and effective versus GE in patients with mPC.Patients and methodsPreviously untreated mPC patients were randomised to receive G (1000 mg/m², days 1, 8, 15) + E (100 mg/day, days 1–28) + C (1660 mg/m², days 1–21) or GE, q4 weeks, until progression or unacceptable toxicity. Primary end-point: progression-free survival (PFS); secondary end-points: overall survival (OS), response rate, relationship of rash with PFS/OS and safety.Results120 patients were randomised, median age 63 years, ECOG status 0/1/2 33%/58%/8%; median follow-up 16.5 months. Median PFS in the gemcitabine–erlotinib–capecitabine (GEC) and GE arms was 4.3 and 3.8 months, respectively (hazard ratio [HR]: 0.88, 95% confidence interval [CI]: 0.58–1.31; p = 0.52). Median OS in the GEC and GE arms was 6.8 and 7.7 months, respectively (HR: 1.09, 95% CI: 0.72–1.63; p = 0.69). Grade 3/4 neutropenia (GEC 43% versus GE 15%; p = 0.0008) and mucositis (GEC 9% versus GE 0%; p = 0.03) were the only statistically significant differences in grade 3/4 adverse events. PFS and OS were significantly longer in patients with rash (grade ≥1) versus no rash (grade = 0): PFS 5.5 versus 2.0 months (HR = 0.39, 95% CI: 0.26–0.6; p < 0.0001) and OS: 9.5 versus 4.0 months (HR = 0.51, 95% CI: 0.33–0.77; p = 0.0014).ConclusionPFS with GEC was not significantly different to that with GE in patients with mPC. Skin rash strongly predicted erlotinib efficacy.The study was registered with ClinicalTrials.gov: NCT01303029.     

The clinical relevance of indeterminate lung nodules in patients with locally recurrent rectal cancer

AimTo evaluate the clinical relevance of indeterminate lung nodules (ILN) in patients with locally recurrent rectal cancer (LRRC) treated in a tertiary referral centre.MethodsAll patients with LRRC diagnosed between 2000 and 2017 were retrospectively reviewed. Reports of staging chest CT-scans were evaluated for ILN. Patients with distant metastases including lung metastases at time of LRRC diagnosis were excluded. Overall (OS), progression-free survival (PFS) and the cumulative incidence of lung metastases were compared between patients with and without ILN.ResultsIn total 556 patients with LRRC were treated during the study period. In the 243 patients eligible for analysis, 68 (28%) had ILN at LRRC diagnosis. Median OS was 37 months for both the patients with and without ILN (p = 0.37). Median PFS was 14 months for the patients with ILN and 16 months for patients without ILN (p = 0.80). After correction for potential confounding, ILN present at LRRC diagnosis was not associated with impaired OS or PFS (adjusted hazards ratio [95% confidence interval]: 0.81 [0.54–1.22] and 1.09 [0.75–1.59]). The 5-year cumulative incidence of lung metastases was 31% in patients with ILN and 28% in patients without ILN (p = 0.19).ConclusionOur study shows that ILN are present in roughly a quarter of patients with LRRC. No differences in OS, PFS, or the cumulative incidence of lung metastases were found between patients with and without ILN at LRRC diagnosis. These results suggest that ILN are of little to no clinical relevance in patients with LRRC.     

Prognostic factors and treatment outcomes in 444 patients with mucosal melanoma

BackgroundMucosal melanoma (MM) is a rare but diverse cancer entity. Prognostic factors are not well established for Caucasians with MM.Patients and methodsWe analysed the disease course of 444 patients from 15 German skin cancer centres. Disease progression was determined with the cumulative incidence function. Survival times were estimated with the Kaplan–Meier method. Prognostic parameters were identified with multivariate Cox regression analysis.ResultsCommon anatomic sites of primary tumours were head and neck (MMHN, 37.2%), female genital tract (MMFG, 30.4%) and anorectal region (MMAN, 21.8%). MMAN patients showed the highest vertical tumour thickness (p = 0.001), had a more advanced nodal status (p = 0.014) and a higher percentage of metastatic disease (p = 0.001) at diagnosis. Mutations of NRAS (13.8%), KIT (8.6%) and BRAF (6.4%) were evenly distributed across all tumour site groups. Local relapses were observed in 32.4% and most commonly occurred in the MMHN group (p = 0.016). Male gender (p = 0.047), advanced tumour stage (p = 0.001), nodal disease (p = 0.001) and incomplete resection status (p = 0.001) were independent risk factors for disease progression. Overall survival (OS) was highest in the MMFG group (p = 0.030) and in patients without ulceration (p = 0.004). Multivariate risk factors for OS were M stage at diagnosis (p = 0.002) and incomplete resection of the primary tumour (p = 0.001).ConclusionIn this large series of MM patients in a European population, anorectal MM was associated with the poorest prognosis.     

Daratumumab,Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Patients With Previously Treated Multiple Myeloma: Three-year Follow-up of CASTOR

BackgroundIn the phase III CASTOR study in relapsed or refractory multiple myeloma, daratumumab, bortezomib, and dexamethasone (D-Vd) demonstrated significant clinical benefit versus Vd alone. Outcomes after 40.0 months of median follow-up are discussed.Patients and MethodsEligible patients had received ≥ 1 line of treatment and were administered bortezomib (1.3 mg/m²) and dexamethasone (20 mg) for 8 cycles with or without daratumumab (16 mg/kg) until disease progression.ResultsOf 498 patients in the intent-to-treat (ITT) population (D-Vd, n = 251; Vd, n = 247), 47% had 1 prior line of treatment (1PL; D-Vd, n = 122; Vd, n = 113). Median progression-free survival (PFS) was significantly prolonged with D-Vd versus Vd in the ITT population (16.7 vs. 7.1 months; hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.25-0.40; P < .0001) and the 1PL subgroup (27.0 vs. 7.9 months; HR, 0.22; 95% CI, 0.15-0.32; P < .0001). In lenalidomide-refractory patients, the median PFS was 7.8 versus 4.9 months (HR, 0.44; 95% CI, 0.28-0.68; P = .0002) for D-Vd (n = 60) versus Vd (n = 81). Minimal residual disease (MRD)–negativity rates (10⁻⁵) were greater with D-Vd versus Vd (ITT: 14% vs. 2%; 1PL: 20% vs. 3%; both P < .0001). PFS2 was significantly prolonged with D-Vd versus Vd (ITT: HR, 0.48; 95% CI, 0.38-0.61; 1PL: HR, 0.35; 95% CI, 0.24-0.51; P < .0001). No new safety concerns were observed.ConclusionAfter 3 years, D-Vd maintained significant benefits in patients with relapsed or refractory multiple myeloma with a consistent safety profile. D-Vd provided the greatest benefit at first relapse and increased MRD-negativity rates.     

Incidence of chemotherapy-induced nausea and vomiting associated with docetaxel and cyclophosphamide in early breast cancer patients and aprepitant efficacy as salvage therapy. Results from the Spanish Breast Cancer Group/2009-02 study

BackgroundDocetaxel–cyclophosphamide (TC) has become a common regimen in moderate-high-risk early breast cancer (EBC), but the incidence of chemotherapy-induced nausea and vomiting (CINV) with this regimen is not well established. This trial investigates the effect of guideline-consistent prophylaxis on CINV related to TC regimen and explores the efficacy of aprepitant among resistant patients.Patients and MethodsThis prospective multicentre study enrolled 212 chemotherapy-naïve EBC patients receiving T-75 mg/m² and C-600 mg/m². Antiemetic therapy on the first cycle consisted of dexamethasone for 3 d plus 5-hydroxytryptamine (5-HT₃) antagonists on day 1, according to Multinational Association of Supportive Care in Cancer guidelines. The primary end-point was complete response (CR) (no emesis and no need of rescue treatment within the initial 120 h). Patients failing CR on cycle 1 entered in a single-arm study exploring the efficacy of aprepitant on the second cycle. Patients' diaries and Functional Living Index-Emesis (FLIE) questionnaires were collected in cycles 1 and 2.ResultsAmong the 185 evaluable patients on cycle 1, 161 (87%, 95% confidence interval [CI]: 82.2–91.8) achieved a CR. Twenty-three patients received aprepitant on cycle 2, and 12 reached a CR (52.2%, 95% CI: 31.8–72.6). The absence of CR had a very substantial impact on quality of life on cycles 1 (FLIE before and after: 23.8–38.1, p = 0.0124) and 2 (18.3–42.9, p = 0.0059).ConclusionsGuideline-consistent antiemetic prophylaxis for the TC regimen is associated with a low incidence of CINV. Aprepitant is effective as secondary prevention of CINV and should be considered as rescue therapy in patients treated with moderate emetogenic chemotherapy.