Category Archives: J Clin Oncol

Interim Fluorodeoxyglucose Positron Emission Tomography-Adapted Therapy Is Not an Efficient Approach to Improving Outcome in Early-Stage Hodgkin Lymphoma.






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Interim Fluorodeoxyglucose Positron Emission Tomography-Adapted Therapy Is Not an Efficient Approach to Improving Outcome in Early-Stage Hodgkin Lymphoma.
J Clin Oncol. 2017 Jul 06;:JCO2017733816
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The Sound of Silence: A Proxy for Platinum Toxicity.






The Sound of Silence: A Proxy for Platinum Toxicity.
J Clin Oncol. 2016 Jul 5;
Authors: Oldenburg J, Gietema JA
PMID: 27382103 [PubMed – as supplied by publisher] Continue reading






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Randomized Comparison of Surveillance Intervals in Familial Colorectal Cancer.






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Randomized Comparison of Surveillance Intervals in Familial Colorectal Cancer.

J Clin Oncol. 2015 Nov 2;

Authors: Hennink SD, van der Meulen-de Jong AE, Wolterbeek R, Crobach AS, Becx MC, Crobach WF, van Haastert M, Ten Hove WR, Kleibeuker JH, Meijssen MA, Nagengast FM, Rijk MC, Salemans JM, Stronkhorst A, Tuynman HA, Vecht J, Verhulst ML, de Vos Tot Nederveen Cappel WH, Walinga H, Weinhardt OK, Westerveld D, Witte AM, Wolters HJ, Cats A, Veenendaal RA, Morreau H, Vasen HF

Abstract
PURPOSE: Colonoscopic surveillance is recommended for individuals with familial colorectal cancer (CRC). However, the appropriate screening interval has not yet been determined. The aim of this randomized trial was to compare a 3-year with a 6-year screening interval.
PATIENTS AND METHODS: Individuals between ages 45 and 65 years with one first-degree relative with CRC age < 50 years or two first-degree relatives with CRC were selected. Patients with zero to two adenomas at baseline were randomly assigned to one of two groups: group A (colonoscopy at 6 years) or group B (colonoscopy at 3 and 6 years). The primary outcome measure was advanced adenomatous polyps (AAPs). Risk factors studied included sex, age, type of family history, and baseline endoscopic findings.
RESULTS: A total of 528 patients were randomly assigned (group A, n = 262; group B, n = 266). Intention-to-treat analysis showed no significant difference in the proportion of patients with AAPs at the first follow-up examination at 6 years in group A (6.9%) versus 3 years in group B (3.5%). Also, the proportion of patients with AAPs at the final follow-up examination at 6 years in group A (6.9%) versus 6 years in group B (3.4%) was not significantly different. Only AAPs at baseline was a significant predictor for the presence of AAPs at first follow-up. After correction for the difference in AAPs at baseline, differences between the groups in the rate of AAPs at first follow-up and at the final examination were statistically significant.
CONCLUSION: In view of the relatively low rate of AAPs at 6 years and the absence of CRC in group A, we consider a 6-year surveillance interval appropriate. A surveillance interval of 3 years might be considered in patients with AAPs and patients with ≥ three adenomas.

PMID: 26527788 [PubMed – as supplied by publisher]

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Advances in Radiotherapy for Head and Neck Cancer.






Advances in Radiotherapy for Head and Neck Cancer.

J Clin Oncol. 2015 Sep 8;

Authors: Grégoire V, Langendijk JA, Nuyts S

Abstract
Over the last few decades, significant improvements have been made in the radiotherapy (RT) treatment of head and neck malignancies. The progressive introduction of intensity-modulated RT and the use of multimodality imaging for target volume and organs at risk delineation, together with the use of altered fractionation regimens and concomitant administration of chemotherapy or targeted agents, have accompanied efficacy improvements in RT. Altogether, such improvements have translated into improvement in locoregional control and overall survival probability, with a decrease in the long-term adverse effects of RT and an improvement in quality of life. Further progress in the treatment of head and neck malignancies may come from a better integration of molecular imaging to identify tumor subvolumes that may require additional radiation doses (ie, dose painting) and from treatment adaptation tracing changes in patient anatomy during treatment. Proton therapy generates even more exquisite dose distribution in some patients, thus potentially further improving patient outcomes. However, the clinical benefit of these approaches, although promising, for patients with head and neck cancer need to be demonstrated in prospective randomized studies. In this context, our article will review some of these advances, with special emphasis on target volume and organ-at-risk delineation, use of molecular imaging for tumor delineation, dose painting for dose escalation, dose adaptation throughout treatment, and potential benefit of proton therapy.

PMID: 26351354 [PubMed – as supplied by publisher]

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Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia.






Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia.
J Clin Oncol. 2015 Aug 24;
Authors: Zwaan CM, Kolb EA, Reinhardt D, Abrahamsson J, Adachi S, Aplenc R, De Bont ES, De Moerloose B, Dworzak M… Continue reading






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Bias Correction Methods Explain Much of the Variation Seen in Breast Cancer Risks of BRCA1/2 Mutation Carriers.






Bias Correction Methods Explain Much of the Variation Seen in Breast Cancer Risks of BRCA1/2 Mutation Carriers.
J Clin Oncol. 2015 Jul 6;
Authors: Vos JR, Hsu L, Brohet RM, Mourits MJ, de Vries J, Malone KE, Oosterwi… Continue reading






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Antibody Positron Emission Tomography Imaging in Anticancer Drug Development.






Antibody Positron Emission Tomography Imaging in Anticancer Drug Development.

J Clin Oncol. 2015 Mar 16;

Authors: Lamberts LE, Williams SP, Terwisscha van Scheltinga AG, Lub-de Hooge MN, Schröder CP, Gietema JA, Brouwers AH, de Vries EG

Abstract
More than 50 monoclonal antibodies (mAbs), including several antibody-drug conjugates, are in advanced clinical development, forming an important part of the many molecularly targeted anticancer therapeutics currently in development. Drug development is a relatively slow and expensive process, limiting the number of drugs that can be brought into late-stage trials. Development decisions could benefit from quantitative biomarkers, enabling visualization of the tissue distribution of (potentially modified) therapeutic mAbs to confirm effective whole-body target expression, engagement, and modulation and to evaluate heterogeneity across lesions and patients. Such biomarkers may be realized with positron emission tomography imaging of radioactively labeled antibodies, a process called immunoPET. This approach could potentially increase the power and value of early trials by improving patient selection, optimizing dose and schedule, and rationalizing observed drug responses. In this review, we summarize the available literature and the status of clinical trials regarding the potential of immunoPET during early anticancer drug development.

PMID: 25779566 [PubMed – as supplied by publisher]

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Pathologic Findings at Risk-Reducing Surgery.






Pathologic Findings at Risk-Reducing Surgery.
J Clin Oncol. 2015 Mar 2;
Authors: Mourits MJ, de Bock GH, Hollema H
PMID: 25732172 [PubMed – as supplied by publisher]

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Magnetic Resonance Imaging Improves Breast Screening Sensitivity in BRCA Mutation Carriers Age ≥ 50 Years: Evidence From an Individual Patient Data Meta-Analysis.






Magnetic Resonance Imaging Improves Breast Screening Sensitivity in BRCA Mutation Carriers Age ≥ 50 Years: Evidence From an Individual Patient Data Meta-Analysis.

J Clin Oncol. 2014 Dec 22;

Authors: Phi X, Houssami N, Obdeijn I, Warner E, Sardanelli F, Leach MO, Riedl CC, Trop I, Tilanus-Linthorst MM, Mandel R, Santoro F, Kwan-Lim G, Helbich TH, de Koning HJ, Van den Heuvel ER, de Bock GH

Abstract
PURPOSE: There is no consensus on whether magnetic resonance imaging (MRI) should be included in breast screening protocols for women with BRCA1/2 mutations age ≥ 50 years. Therefore, we investigated the evidence on age-related screening accuracy in women with BRCA1/2 mutations using individual patient data (IPD) meta-analysis.
PATIENTS AND METHODS: IPD were pooled from six high-risk screening trials including women with BRCA1/2 mutations who had completed at least one screening round with both MRI and mammography. A generalized linear mixed model with repeated measurements and a random effect of studies estimated sensitivity and specificity of MRI, mammography, and the combination in all women and specifically in those age ≥ 50 years.
RESULTS: Pooled analysis showed that in women age ≥ 50 years, screening sensitivity was not different from that in women age < 50 years, whereas screening specificity was. In women age ≥ 50 years, combining MRI and mammography significantly increased screening sensitivity compared with mammography alone (94.1%; 95% CI, 77.7% to 98.7% v 38.1%; 95% CI, 22.4% to 56.7%; P < .001). The combination was not significantly more sensitive than MRI alone (94.1%; 95% CI, 77.7% to 98.7% v 84.4%; 95% CI, 61.8% to 94.8%; P = .28). Combining MRI and mammography in women age ≥ 50 years resulted in sensitivity similar to that in women age < 50 years (94.1%; 95% CI, 77.7% to 98.7% v 93.2%; 95% CI, 79.3% to 98%; P = .79).
CONCLUSION: Addition of MRI to mammography for screening BRCA1/2 mutation carriers age ≥ 50 years improves screening sensitivity by a magnitude similar to that observed in younger women. Limiting screening MRI in BRCA1/2 carriers age ≥ 50 years should be reconsidered.

PMID: 25534390 [PubMed – as supplied by publisher]

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Lynch Syndrome Caused by Germline PMS2 Mutations: Delineating the Cancer Risk.






Lynch Syndrome Caused by Germline PMS2 Mutations: Delineating the Cancer Risk.

J Clin Oncol. 2014 Dec 15;

Authors: Ten Broeke SW, Brohet RM, Tops CM, van der Klift HM, Velthuizen ME, Bernstein I, Capellá Munar G, Gomez Garcia E, Hoogerbrugge N, Letteboer TG, Menko FH, Lindblom A, Mensenkamp AR, Moller P, van Os TA, Rahner N, Redeker BJ, Sijmons RH, Spruijt L, Suerink M, Vos YJ, Wagner A, Hes FJ, Vasen HF, Nielsen M, Wijnen JT

Abstract
PURPOSE: The clinical consequences of PMS2 germline mutations are poorly understood compared with other Lynch-associated mismatch repair gene (MMR) mutations. The aim of this European cohort study was to define the cancer risk faced by PMS2 mutation carriers.
METHODS: Data were collected from 98 PMS2 families ascertained from family cancer clinics that included a total of 2,548 family members and 377 proven mutation carriers. To adjust for potential ascertainment bias, a modified segregation analysis model was used to calculate colorectal cancer (CRC) and endometrial cancer (EC) risks. Standardized incidence ratios (SIRs) were calculated to estimate risks for other Lynch syndrome-associated cancers.
RESULTS: The cumulative risk (CR) of CRC for male mutation carriers by age 70 years was 19%. The CR among female carriers was 11% for CRC and 12% for EC. The mean age of CRC development was 52 years, and there was a significant difference in mean age of CRC between the probands (mean, 47 years; range, 26 to 68 years) and other family members with a PMS2 mutation (mean, 58 years; range, 31 to 86 years; P < .001). Significant SIRs were observed for cancers of the small bowel, ovaries, breast, and renal pelvis.
CONCLUSION: CRC and EC risks were found to be markedly lower than those previously reported for the other MMR. However, these risks embody the isolated risk of carrying a PMS2 mutation, and it should be noted that we observed a substantial variation in cancer phenotype within and between families, suggesting the influence of genetic modifiers and lifestyle factors on cancer risks.

PMID: 25512458 [PubMed – as supplied by publisher]

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Trastuzumab-associated cardiac events at 8 years of median follow-up in the Herceptin Adjuvant trial (BIG 1-01).






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Trastuzumab-associated cardiac events at 8 years of median follow-up in the Herceptin Adjuvant trial (BIG 1-01).

J Clin Oncol. 2014 Jul 10;32(20):2159-65

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International Society of Geriatric Oncology Consensus on Geriatric Assessment in Older Patients With Cancer.






International Society of Geriatric Oncology Consensus on Geriatric Assessment in Older Patients With Cancer.
J Clin Oncol. 2014 Jul 28;
Authors: Wildiers H, Heeren P, Puts M, Topinkova E, Janssen-Heijnen ML, Exterman… Continue reading






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Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial.






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Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of…

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Confirmation of the mantle-cell lymphoma International Prognostic Index in randomized trials of the European Mantle-Cell Lymphoma Network.






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Confirmation of the mantle-cell lymphoma International Prognostic Index in randomized trials of the European Mantle-Cell Lymphoma Network.

J Clin Oncol….

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Vemurafenib-Induced Disseminated Intravascular Coagulation in Metastatic Melanoma.






Vemurafenib-Induced Disseminated Intravascular Coagulation in Metastatic Melanoma.

J Clin Oncol. 2014 Apr 28;

Authors: van den Brom RR, Mäkelburg AB, Schröder CP, de Vries EG, Hospers GA

PMID: 24778390 [PubMed – as supplied by publisher]

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Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials.






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Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials.

J Clin Oncol. 2014 Feb 10;32(5):385-91

Authors: Oppedijk V, van der Gaast A, van Lanschot JJ, van Hagen P, van Os R, van Rij CM, van der Sangen MJ, Beukema JC, Rütten H, Spruit PH, Reinders JG, Richel DJ, van Berge Henegouwen MI, Hulshof MC

Abstract
PURPOSE: To analyze recurrence patterns in patients with cancer of the esophagus or gastroesophageal junction treated with either preoperative chemoradiotherapy (CRT) plus surgery or surgery alone.
PATIENTS AND METHODS: Recurrence pattern was analyzed in patients from the previously published CROSS I and II trials in relation to radiation target volumes. CRT consisted of five weekly courses of paclitaxel and carboplatin combined with a concurrent radiation dose of 41.4 Gy in 1.8-Gy fractions to the tumor and pathologic lymph nodes with margin.
RESULTS: Of the 422 patients included from 2001 to 2008, 418 were available for analysis. Histology was mostly adenocarcinoma (75%). Of the 374 patients who underwent resection, 86% were allocated to surgery and 92% to CRT plus surgery. On January 1, 2011, after a minimum follow-up of 24 months (median, 45 months), the overall recurrence rate in the surgery arm was 58% versus 35% in the CRT plus surgery arm. Preoperative CRT reduced locoregional recurrence (LRR) from 34% to 14% (P < .001) and peritoneal carcinomatosis from 14% to 4% (P < .001). There was a small but significant effect on hematogenous dissemination in favor of the CRT group (35% v 29%; P = .025). LRR occurred in 5% within the target volume, in 2% in the margins, and in 6% outside the radiation target volume. In 1%, the exact site in relation to the target volume was unclear. Only 1% had an isolated infield recurrence after CRT plus surgery.
CONCLUSION: Preoperative CRT in patients with esophageal cancer reduced LRR and peritoneal carcinomatosis. Recurrence within the radiation target volume occurred in only 5%, mostly combined with outfield failures.

PMID: 24419108 [PubMed – indexed for MEDLINE]

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Easy navigating through the forest of survivorship care.






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Easy navigating through the forest of survivorship care.

J Clin Oncol. 2014 Jan 1;32(1):61-2

Authors: Boer H, Nuver J, Lefrandt JD, Duijzer AW, Bunskoek…

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Primary granulocyte colony-stimulating factor prophylaxis during the first two cycles only or throughout all chemotherapy cycles in patients with breast cancer at risk for febrile neutropenia.






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Primary granulocyte colony-stimulating factor prophylaxis during the first two cycles only or throughout all chemotherapy cycles in patients with breast cancer at risk for…

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Cost effectiveness of primary pegfilgrastim prophylaxis in patients with breast cancer at risk of febrile neutropenia.






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Cost effectiveness of primary pegfilgrastim prophylaxis in patients with breast cancer at risk of febrile neutropenia.

J Clin Oncol. 2013 Dec 1;31(34):4283-9

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Long-term cardiovascular mortality in patients with differentiated thyroid carcinoma: an observational study.






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Long-term cardiovascular mortality in patients with differentiated thyroid carcinoma: an observational study.

J Clin Oncol. 2013 Nov 10;31(32):4046-53

Authors: Klein Hesselink EN, Klein Hesselink MS, de Bock GH, Gansevoort RT, Bakker SJ, Vredeveld EJ, van der Horst-Schrivers AN, van der Horst IC, Kamphuisen PW, Plukker JT, Links TP, Lefrandt JD

Abstract
PURPOSE: The primary aim was to study the risk of cardiovascular mortality in patients with differentiated thyroid carcinoma (DTC). Secondary aims were to evaluate all-cause mortality and explore the relation between thyroid-stimulating hormone (TSH; also known as thyrotropin) level and these outcome parameters.
PATIENTS AND METHODS: Subjects from two cohorts were retrospectively compared by Cox regression analyses; 524 patients with DTC and 1,572 sex- and age-matched controls from a large population-based study in the same geographic region.
RESULTS: Mean age plus or minus standard deviation was 49 ± 14 years. Median follow-up was 8.5 years (interquartile range [IQR], 4.1 to 15.9 years) for patients with DTC and 10.5 years (IQR, 9.9 to 10.9 years) for controls. One hundred patients with DTC (19.1%) died, 22 (4.2%) as a result of cardiovascular disease, 39 (7.4%) as a result of DTC, and 39 (7.4%) as a result of other/unknown causes. Eighty-five controls (5.4%) died, 24 (1.5%) as a result of cardiovascular disease and 61 (3.9%) as a result of other/unknown causes. Patients with DTC had an increased risk of cardiovascular and all-cause mortality (hazard ratios [HRs], 3.35 [95% CI, 1.66 to 6.74] and 4.40 [95% CI, 3.15 to 6.14], respectively, adjusted for age, sex, and cardiovascular risk factors). Within the DTC group, TSH level was predictive for cardiovascular mortality; the adjusted HR was 3.08 (95% CI, 1.32 to 7.21) for each 10-fold decrease in geometric mean TSH level.
CONCLUSION: The risk of cardiovascular and all-cause mortality is increased in patients with DTC, independent of age, sex, and cardiovascular risk factors. A lower TSH level is associated with increased cardiovascular mortality, supporting the current European Thyroid Association and the American Thyroid Association guidelines of tempering TSH suppression in patients with low risk of cancer recurrence. Furthermore, patients with DTC may benefit from assessment and treatment of cardiovascular risk factors.

PMID: 24101052 [PubMed – indexed for MEDLINE]

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