scholarly journals Serial Cancer Development Three Times in a Patient with Fanconi Anemia

2021 ◽  
pp. 1168-1174
Author(s):  
Katsuya Yanagisawa ◽  
Toshimichi Horiuchi ◽  
Akemi Matsuo ◽  
Hiroshi Kuraishi ◽  
Hidetoshi Satomi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Solid Tumors ◽  
Fanconi Anemia ◽  
Cell Lung Cancer ◽  
Bone Marrow Failure ◽  
Nonsmall Cell Lung Cancer ◽  
Cancer Development ◽  
Hematopoietic Stem ◽  
Anal Squamous Cell Carcinoma ◽  
Increased Risk

Fanconi anemia (FA) is characterized clinically by bone marrow failure, congenital malformations, sensitivity to DNA cross-linking agents, and increased risk of malignancy. Hematological cancer is the best-described malignancy in patients with FA, but the susceptibility to the development of solid tumors is also well documented, especially after hematopoietic stem cell transplantation (HSCT). With regard to the development of solid tumors in patients with FA, head and neck, esophageal, and anal squamous cell carcinoma are well known, but reports of lung cancer are extremely rare. Here, we describe an FA patient with a history of HSCT that developed 3 serial cancers – oral, esophageal, and nonsmall cell lung cancer – over a period of 6 years. The third lesion was nonsmall cell lung cancer and its location corresponded closely to the field of irradiation treatment for prior esophageal cancer. The occurrence of lung cancer in patients with FA is uncommon, but FA patients should be screened regularly and serially. Our case also indicated the importance of the irradiated field as a location for subsequent cancer development.

Cancer Risks in Fanconi Anemia: Experience of the German Fanconi Anemia (GEFA) Registry.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 995-995
Author(s):  
Philip S. Rosenberg ◽  
Blanche P. Alter ◽  
Wolfram Ebell
Keyword(s):  
Bone Marrow ◽  
Solid Tumors ◽  
Fanconi Anemia ◽  
North American ◽  
Cumulative Incidence ◽  
Age Of Onset ◽  
Bone Marrow Failure ◽  
Significant Risk ◽  
North American Population ◽  
Increased Risk

Abstract OBJECTIVE: Acute Myeloid Leukemia (AML) and solid tumors (ST) occur frequently in Fanconi Anemia (FA). Our objective was to characterize the age of onset of cancer and identify any neoplasms occurring in excess. METHODS: We analyzed data from the German Fanconi Anemia (GEFA) Registry, a retrospective cohort. For competing adverse events of bone marrow failure (BMF), AML, and ST, we determined cause-specific hazards and cumulative incidence curves. We calculated the ratio of observed to expected cancers (O/E ratio) in GEFA compared to age- and sex-matched persons from the general North American population. We studied outcomes after bone marrow transplantation (BMT) using survival analysis. RESULTS: In GEFA, 182 patients contributed 2548 person-years of observation prior to BMT; 63 had BMF as the first adverse event, 15 had AML, and 10 had ST. The cumulative incidence by age 50 was 48% for BMF and 29% for ST. The cumulative incidence by age 20 was 9% for AML. The hazard of BMF peaked at 4%/y at age 10. The hazard of AML increased to 1.6%/y at age 20. The hazard of ST increased from 1%/y at age 20, to 5%/y at age 40, to ~10%/y at age 50. The O/E ratio was 45 for all cancers, 24 for all solid tumors, and 926 for AML; these increased risks were statistically significant. Significantly elevated O/E ratios were observed for esophagus (6346), vulva (2436), oral cavity and pharynx (121), breast (34), and brain (23) cancers. Forty-eight patients had BMT prior to cancer. Subsequently, there were 20 deaths and 3 malignancies in 216 person-years. The 3 malignancies (tongue, liver, and esophagus) occurred 2, 16, and 17 years after mismatched, matched, and matched transplant at ages 13, 23, and 34, respectively. The age-specific hazard of ST was 3.8-fold higher in transplanted versus untransplanted patients; this increased risk was not significant (P = 0.11). During 2000–2004, none of 5 patients with matched, and 3 of 18 patients with mismatched donors, died during the period from 0 – 6 months. In patients with matched donors, acute and chronic GVH were significant risk factors for death beyond 6 months. CONCLUSIONS: Absolute and relative risks of cancer in GEFA are quantitatively similar to previously reported estimates from the North American Survey. Outcomes after transplantation in GEFA are comparable to the Hôpital St Louis Cohort. Our prior observation that FA patients who survive BMF are at extraordinary risk of specific ST has been replicated.

Interleukin 17A Polymorphism Elevates Gene Expression and Is Associated with Increased Risk of Nonsmall Cell Lung Cancer

2015 ◽  
Vol 34 (1) ◽  
pp. 63-68 ◽  
Author(s):  
Sensen Cheng ◽  
Zhulin Shao ◽  
Xiuchun Liu ◽  
Liangjun Guo ◽  
Xia Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Cell Lung Cancer ◽  
Nonsmall Cell Lung Cancer ◽  
Interleukin 17A ◽  
Increased Risk

KIT Blockade Is Sufficient to Sustain Donor Hematopoietic Stem Cell Engraftment in Fanconi Anemia Mice

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1206-1206
Author(s):  
Shanmuganathan Chandrakasan ◽  
Rajeswari Jayavaradhan ◽  
Ernst John ◽  
Archana Shrestha ◽  
Phillip Dexheimer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Fanconi Anemia ◽  
Conflicts Of Interest ◽  
Bone Marrow Failure ◽  
Conditioning Regimen ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Increased Risk

Abstract Background: Fanconi anemia (FA) is the most common cause of inherited bone marrow failure (BMF). Currently, the only curative option for the BMF in FA is an allogenic hematopoietic stem cell transplant (HSCT). However, due to the underlying DNA repair defect, FA patients poorly tolerate alkylating chemotherapy or irradiation based conditioning, which is necessary for donor engraftment. However, this results in significant short and long term morbidity/mortality and augments the inherent increased risk of malignancies in FA patients. To overcome the adverse effects associated with alkylating conditioning agents, alternate experimental approaches exploiting the inherent hematopoietic stem cell (HSC) defect in FA are of utmost clinical necessity. Objective: To develop a safe KIT blocking antibody (KIT-Ab) based HSCT conditioning regimen for FA that does not involve chemotherapy or irradiation. Method: High purity KIT-Ab was made from the ACK2 hybridoma and its specificity to KIT binding was validated using mast cell assay. Baseline peripheral blood cells and the bone marrow hematopoietic stem and progenitor cell (HSPC) compartment (Lin-Kit+Sca+ and Lin-Kit+Sca+CD150+CD48- cells) of FANCA-/- and FANCD2-/- murine models were analyzed. Mechanistic studies using sorted FA bone marrow HSPC were performed ex vivo. This was followed by definitive primary and secondary transplants experiments following injection of KIT-Ab. Results: Several features of FA hematopoietic stem/progenitor cells (HSPC) suggested their susceptibility to KIT-Ab blockade-mediated killing: (a) Expression of KIT was significantly lower in FANCA-/- HSPC, while expression of its ligand was higher in bone marrow stroma; (b) Moreover, genes associated with apoptosis/senescence, stress and inflammatory signaling that were upregulated in WT-HSPC following KIT-Ab blockade, were upregulated in FANCA-/- HSPC at baseline; (c) Furthermore, FANCA-/- HSPC demonstrated increased susceptibility to KIT-Ab mediated apoptosis and had a reduced proliferative capacity. In-vivo studies following ACK2 injection showed a marked reduction of colony-forming units (CFU-C) from both FANCA-/- and FANCD2-/- mice one week following injection, when compared to WT mice (48% and 76% decrease in CFU-C, respectively). Based on these findings, we evaluated the role of ACK2 as a sole HSCT conditioning regimen in FANCA-/- and FANCD2-/- mice. Indeed, definitive HSCT in both FANCA-/- and FANCD2-/- mice using KIT-Ab based conditioning resulted in donor HSC engraftment with multi-lineage chimerism, which progressively increased to 22-24% by 4-months, and was sustained in secondary transplants. Overall, we show that KIT-blockade alone is an adequate non-genotoxic HSPC-targeted conditioning in FA mice, and its clinical translation could circumvent the extensive transplant-related morbidity/mortality in this disease. Disclosures No relevant conflicts of interest to declare.

scholarly journals Wnt Pathway Activation Predicts Increased Risk of Tumor Recurrence in Patients With Stage I Nonsmall Cell Lung Cancer

2013 ◽  
Vol 257 (3) ◽  
pp. 548-554 ◽  
Author(s):  
Mark Shapiro ◽  
Gal Akiri ◽  
Cynthia Chin ◽  
Juan P. Wisnivesky ◽  
Mary B. Beasley ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Lung Cancer ◽  
Tumor Recurrence ◽  
Wnt Pathway ◽  
Nonsmall Cell Lung Cancer ◽  
Stage I ◽  
Pathway Activation ◽  
Increased Risk

scholarly journals Complete metabolic response in patients with advanced nonsmall cell lung cancer with prolonged response to immune checkpoint inhibitor therapy

2021 ◽  
Vol 9 (3) ◽  
pp. e002262
Author(s):  
Justin Ferdinandus ◽  
Martin Metzenmacher ◽  
Lukas Kessler ◽  
Lale Umutlu ◽  
Clemens Aigner ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Lung Cancer ◽  
Metabolic Response ◽  
Standard Of Care ◽  
Nonsmall Cell Lung Cancer ◽  
Published Data ◽  
Complete Metabolic Response ◽  
Positron Emission ◽  
Checkpoint Inhibitor Therapy

IntroductionImmunotherapy is the new standard of care in advanced nonsmall cell lung cancer (NSCLC). Recently published data show that treatment discontinuation after 12 months of nivolumab treatment is associated with shorter survival. Therefore, the ideal duration of immunotherapy remains unclear, and finding markers of beneficial outcomes is of great importance. Here, we determine the proportion of complete metabolic responses (CMR) in patients who have not progressed after 24 months of immunotherapy.MethodsThis is a retrospective analysis of 45 patients with positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose imaging for assessment of residual metabolic activity after at least 24 months. CMR was defined as uptake in tumor lesions below background levels, using mediastinum as a reference. ResultsOut of 45 patients, 29 patients had a CMR (64%). CMR was observed more frequently in non-first-line patients. Patients with CMR were younger (median 65.7 vs 75.5, p=0.03). Fourteen patients with CMR have discontinued therapy and have not progressed until time of analysis; however, median follow-up was only 5.6 (range 0.8–17.0) months.ConclusionAfter a minimum of 24 months of palliative immunotherapy for NSCLC, CMR occurred in almost two thirds of patients. Potentially, achievement of CMR might identify patients, for whom palliative immunotherapy may be safely discontinued.

scholarly journals Aberrantp16 promoter methylation in smokers and former smokers with nonsmall cell lung cancer

2003 ◽  
Vol 106 (6) ◽  
pp. 913-918 ◽  
Author(s):  
Sonata Jarmalaite ◽  
Annamaria Kannio ◽  
Sisko Anttila ◽  
Juozas R. Lazutka ◽  
Kirsti Husgafvel-Pursiainen
Keyword(s):  
Lung Cancer ◽  
Cell Lung Cancer ◽  
Promoter Methylation ◽  
Nonsmall Cell Lung Cancer ◽  
Former Smokers
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