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Background Treatment for local and locoregional recurrence or second head-and-neck (H&N) cancers after previous radiotherapy is challenging, and re-irradiation carries a significantly increased risk for radiotherapy-related normal tissue toxicities and treatment failure due to a radioresistant tumor phenotype. Here, we analyzed re-irradiation management and outcomes in patients with recurrent or second primary H&N carcinoma using state-of-the-art diagnostic procedures and radiotherapy techniques. Methods Between 2010 and 2019, 48 patients with recurrent or second primary H&N carcinoma received re-radiotherapy at the University of Freiburg Medical Center and were included in this study. Overall survival (OS) and progression-free survival (PFS) were calculated with the Kaplan-Meier method, and univariate Cox-regression analyses were performed to assess the effects of clinico-pathological factors on treatment outcomes. Acute and chronic treatment-related toxicities were quantified using the Common Terminology Criteria for Adverse Events (CTCAE v4.03). Results Thirty-one patients (64.6%) received definitive and 17 (35.4%) adjuvant radiotherapy. Simultaneous chemotherapy was administered in 28 patients (58.3%) with cetuximab as the most commonly used systemic agent ( n  = 17, 60.7%). After a median time of 17 months (range 4 months to 176 months) between first and second radiotherapy, patients were re-irradiated with a median of 58.4 Gy and a treatment completion rate of 87.5% ( n  = 42). Median OS was 25 months with a 1-year OS amounting to 62.4%, and median PFS was 9 months with a 1-year PFS of 37.6%. Univariate analyses demonstrated that both a lower rT-status and a radiotherapy boost were associated with improved OS ( p  < 0.05). There was a trend towards superior OS for patients who received > 50 Gy ( p  = 0.091) and who completed the prescribed radiotherapy ( p  = 0.055). Five patients (10.4%) suffered from at least one grade 3 toxicities, while 9 patients (27.3%) experienced chronic higher-grade toxicities (≥ grade 3) with one (3.0%) grade 4 carotid blowout and one (3.0%) grade 4 osteoradionecrosis. Conclusion Re-irradiation of recurrent or second primary H&N cancer with modern radiation techniques such as intensity-modulated radiotherapy resulted in promising survival rates with acceptable toxicities compared to historical cohorts. Increased re-irradiation doses, utilization of a radiotherapy boost and completion of the re-irradiation treatment were found to result in improved survival.

Background Careful selection of patients with colorectal peritoneal metastases (PM) for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is crucial. It remains unknown whether the time of onset of colorectal PM (synchronous vs metachronous) influences surgical morbidity and survival outcomes after CRS with HIPEC. Methods Patients with histologically proven colorectal PM who underwent CRS with HIPEC between February 2006 and December 2017 in two Dutch tertiary referral hospitals were retrospectively included from a prospectively maintained database. The onset of colorectal PM was classified as synchronous (PM diagnosed at the initiational presentation with colorectal cancer) or metachronous (PM diagnosed after initial curative colorectal resection). Major postoperative complications (Clavien–Dindo grade ≥ 3), overall survival (OS), and disease-free survival (DFS) were compared between patients with synchronous colorectal PM and those with metachronous colorectal PM using Kaplan–Meier analyses, proportional hazard analyses, and a multivariate Cox regression analysis. Results The study enrolled 433 patients, of whom 231 (53%) had synchronous colorectal PM and 202 (47%) had metachronous colorectal PM. The major postoperative complication rate and median OS were similar between the patients with synchronous colorectal PM and those with metachronous colorectal PM (26.8% vs 29.7%; p  = 0.693 and 34 vs 33 months, respectively; p  = 0.819). The median DFS was significantly decreased for the patients with metachronous colorectal PM and those with synchronous colorectal PM (11 vs 15 months; adjusted hazard ratio, 1.63; 95% confidence interval, 1.18–2.26). Conclusions Metachronous onset of colorectal PM is associated with early recurrence after CRS with HIPEC compared with synchronous colorectal PM, without a difference in OS or major postoperative complications. Time to onset of colorectal PM should be taken into consideration to optimize patient selection for this major procedure.

The aims of this study were twofold: to analyze the incidence of patients having synchronous or metachronous bilateral invasive breast cancer (SBBC and MBBC) and to assess the characteristics and outcome compared to those having unilateral breast cancer (UBC). The used data were obtained from our prospective population-based cohort study which had been started in 1983. Bilateral breast cancer (BBC) was categorized as SBBC (≤3 months of the first primary) or MBBC (>3 months after the first primary). The incidence of SBBC was 1 % and that of MBBC 7.0 %. Patients with UBC showed more ductal carcinoma compared to patients with BBC. MBBC status was an independent significant predictor of local failure (HR 1.9; 95 % CI 1.3–2.7). SBBC status was an independent predictor of distant metastases (HR 2.6; 95 % CI 1.4–4.5). Overall survival (OS) was better for MBBC (HR 0.6; 95 % CI 0.4–0.8) and worse for SBBC (HR 2.3; 95 % CI 1.5–3.6) compared to UBC. We noted: (1) MBBC showed a significant higher local failure compared to UBC, (2) SBBC, compared to MBBC and UBC had a significant higher distant metastases rate, (3) disease-specific survival and OS were significantly worse for SBBC compared to UBC and MBBC, and (4) that the OS for MBBC compared to UBC, was significantly better.

Background Radical treatment for oligometastatic non-small-cell lung cancer (NSCLC) has a curative potential for selected patients. The present retrospective study was designed to examine the relevance of synchronous vs. metachronous manifestations as a potential prognostic factor when ablative treatments are performed in oligometastatic disease. Methods Seventy-five patients with radically treated oligometastatic NSCLC were identified, of whom 39 presented with synchronous and 36 with metachronous metastatic manifestations. For patients with synchronous metastases, an additional therapy of the thoracic locoregional disease with a curative intent (either surgery or radiochemotherapy) was required. All patients with metachronous metastases had a documented remission of the primary tumor. Ablative treatment of the complete extent of oligometastatic disease consisted (as a minimum requirement) of either complete surgical resection or definitive ablative stereotactic radiotherapy. A comparative survival analysis of two groups of patients with oligometastatic NSCLC (synchronous vs. metachronous) and a complementary analysis of prognostic factors for the whole group of patients (by means of Cox regression analysis) was performed. Endpoints were median overall and progression-free survival (OS, PFS, respectively). Results Of the 75 patients, 57 presented with a solitary metastasis, in only 7 patients metastastatic lesions were present in ≥2 organs and 66 patients had a Karnofsky performance score (KPS) of 80 % or 90 %. The median follow-up was 54.0 months (95 % CI 28–81), the median OS 21.8 months (16.1–27.6) and the median PFS 13.7 months (9.7–17.6). In univariable Cox regression analysis, no single clinical factor was significantly associated with OS. For PFS both ‘metastatic involvement of ≥2 organs vs. 1 organ’ (hazard ratio (HR) 0.43, 0.23–0.83, p  = 0.012) and a ‘KPS of 90 % vs. 70–80 %’ (HR 4.32, 1.73–10.89, p  = 0.02) were significant prognostic factors as calculated by multivariable analysis. Comparing the cohorts with synchronous ( n  = 39) vs. metachronous oligometastases ( n  = 36), no differences in median OS and PFS were found. Both cohorts were well-balanced except for the KPS, which was significantly superior in patients with synchronous oligometastases. Conclusions Radical treatment of oligometastatic NSCLC was associated with acceptable long-term survival rates in patients with good KPS and it was equally effective for synchronous and metachronous manifestations.

Childhood cancer survivors are at risk for development of subsequent neoplasms of the CNS. Better understanding of the rates, risk factors, and outcomes of subsequent neoplasms of the CNS among survivors of childhood cancer could lead to more informed screening guidelines. Two investigators independently did a systematic search of Medline and Embase (from January, 1966, through March, 2012) for studies examining subsequent neoplasms of the CNS among survivors of childhood cancer. Articles were selected to answer three questions: what is the risk of CNS tumours after radiation to the cranium for a paediatric cancer, compared with the risk in the general population; what are the outcomes in children with subsequent neoplasms of the CNS who received CNS-directed radiation for a paediatric cancer; and, are outcomes of subsequent neoplasms different from primary neoplasms of the same histology? Our search identified 72 reports, of which 18 were included in this Review. These studies reported that childhood cancer survivors have an 8·1–52·3-times higher incidence of subsequent CNS neoplasms compared with the general population. Nearly all cancer survivors who developed a CNS neoplasm had been exposed to cranial radiation, and some studies showed a correlation between radiation dose and risk of subsequent CNS tumours. 5-year survival ranged from 0–19·5% for subsequent high-grade gliomas and 57·3–100% for meningiomas, which are similar rates to those observed in patients with primary gliomas or meningiomas. The quality of evidence was limited by variation in study design, heterogeneity of details regarding treatment and outcomes, limited follow-up, and small sample sizes. We conclude that survivors of childhood cancer who received cranial radiation therapy have an increased risk for subsequent CNS neoplasms. The current literature is insufficient to comment about the potential harms and benefits of routine screening for subsequent CNS neoplasms.

In the current World Health Organization (WHO)-classification, therapy-related myelodysplastic syndromes (t-MDS) are categorized together with therapy-related acute myeloid leukemia (AML) and t-myelodysplastic/myeloproliferative neoplasms into one subgroup independent of morphologic or prognostic features. Analyzing data of 2087 t-MDS patients from different international MDS groups to evaluate classification and prognostication tools we found that applying the WHO classification for p-MDS successfully predicts time to transformation and survival (both p  < 0.001). The results regarding carefully reviewed cytogenetic data, classifications, and prognostic scores confirmed that t-MDS are similarly heterogeneous as p-MDS and therefore deserve the same careful differentiation regarding risk. As reference, these results were compared with 4593 primary MDS (p-MDS) patients represented in the International Working Group for Prognosis in MDS database (IWG-PM). Although a less favorable clinical outcome occurred in each t-MDS subset compared with p-MDS subgroups, FAB and WHO-classification, IPSS-R, and WPSS-R separated t-MDS patients into differing risk groups effectively, indicating that all established risk factors for p-MDS maintained relevance in t-MDS, with cytogenetic features having enhanced predictive power. These data strongly argue to classify t-MDS as a separate entity distinct from other WHO-classified t-myeloid neoplasms, which would enhance treatment decisions and facilitate the inclusion of t-MDS patients into clinical studies.

Key Points Therapy-related myeloid neoplasms (t-MN) arise as a late effect of chemotherapy and/or radiation administered for a primary condition, often a malignant disease, solid organ transplant or autoimmune disease. The majority of t-MN have high-risk cytogenetic features, and the prognosis for patients with t-MN is poor, with a 5-year survival of 10%. Germline mutations in genes associated with an inherited predisposition to cancer have been identified in approximately 20% of patients with t-MN. Chemotherapy and/or radiotherapy promotes clonal selection of pre-existing, mutant haematopoietic stem cells in addition to directly inducing leukaemogenic mutations. The somatic mutations in t-MN are indistinguishable from those occurring in de novo acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). Large chromosomal deletions, such as del(5q) and del(7q), that occur in t-MN do not harbour a single, recessive tumour suppressor gene but instead are part of a contiguous gene syndrome (CGS). Moreover, the genes involved in CGSs on these chromosomes act by haploinsufficiency. An aberrant bone marrow microenvironment directly contributes to the pathogenesis of t-MN. Therapy-related myeloid neoplasms occur as a late complication following chemotherapy and/or radiotherapy administered for a primary condition. In this Review, McNerney et al . discuss recent studies that have improved our understanding of the aetiology of this disease. Therapy-related myeloid neoplasms (t-MN) arise as a late effect of chemotherapy and/or radiation administered for a primary condition, typically a malignant disease, solid organ transplant or autoimmune disease. Survival is measured in months, not years, making t-MN one of the most aggressive and lethal cancers. In this Review, we discuss recent developments that reframe our understanding of the genetic and environmental aetiology of t-MN. Emerging data are illuminating who is at highest risk of developing t-MN, why t-MN are chemoresistant and how we may use this information to treat and ultimately prevent this lethal disease.

Background: Recent therapeutic developments demand for an update of information on natural history, risk factors and prognosis of peritoneal carcinomatosis (PC) of colorectal origin. Therefore, prospective registry data should provide information about incidence, predictors and outcome. Methods: From a prospectively expanded single-institutional database with 2406 consecutive patients with colorectal cancer (CRC), clinical, histological and survival data were analysed for independent risk factors and prognosis. Findings were then stratified to the era of treatment without chemotherapy, 5-Fluorouracil-only and contemporary systemic chemotherapy, respectively. Results: Overall, 256 (10.6%) patients were diagnosed with PC thereof 141 (5.85%) with metachronous PC. Independent risk factors for the development of metachronous PC were age <62 years, N2-status, T4-status, location of the primary in the left colon or appendix. In the era of contemporary systemic chemotherapy, prognosis for PC improved only not-significantly (median survival of 17.9 months vs 7.03 months, P= 0.054). Conclusion: Despite improvement in the overall outcome with prolonged median survival for the complete patient cohort with CRC, those patients with PC have not experienced the same benefit. In the era of contemporary systemic chemotherapy, progress in treatment resulted in only limited survival benefit. Thus, continuous efforts for further therapeutic advancements should be undertaken in these patients diagnosed with PC.

Multiple primary malignant neoplasms are multiple tumors with different pathogenetic origin. They may be synchronous or metachronous. The management of these conditions represents an interesting clinical scenario. A crucial aspect is the decision regarding which tumor to treat initially, and how to schedule further treatments according to individual tumor risk. This process involves a multidisciplinary physician team to ensure favorable outcomes. We describe a case report of a female patient affected by primary synchronous tumors of the breast and pectoral skin, which raised a series of diagnostic, etiological and therapeutic issues persuading us to carry out a critical review of the literature.

Metastatic spread represents the leading cause of disease-related mortality among cancer patients. Many cancer patients suffer from metastatic relapse years or even decades after radical surgery for the primary tumor. This clinical phenomenon is explained by the early dissemination of cancer cells followed by a long period of dormancy. Although dormancy could be viewed as a window of opportunity for therapeutic interventions, dormant disseminated cancer cells and micrometastases, as well as emergent outgrowing macrometastases, exhibit a generalized, innate resistance to chemotherapy and even immunotherapy. This therapeutic pan-resistance, on top of other adaptive responses to targeted agents such as acquired mutations and lineage plasticity, underpins the current difficulties in eradicating cancer. In the present review, we attempt to provide a framework to understand the underlying biology of this major issue.