LIFE09200604007 Tabish - Homi Bhabha National Institute

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CASE REPORT Eben L. Rosenthal, MD, Section Editor SQUAMOUS CELL CARCINOMA OF BASE OF TONGUE IN A PATIENT WITH FANCONI’S ANEMIA TREATED WITH RADIATION THERAPY: CASE REPORT AND REVIEW OF LITERATURE Ashwini Budrukkar, MD, 1 Tanweer Shahid, DNB, 1 Vedang Murthy, MD, 1 Tabish Hussain, MSc, 2 Rita Mulherkar, PhD, 2 Babu Rao Vundinti, PhD, 3 Mandar Deshpande, MS, 4 Manju Sengar, MD, 5 Sarbani Ghosh Laskar, MD, 1 Jai Prakash Agarwal, MD 1 1 Department of Radiation Oncology, Tata Memorial Hospital, Parel, Mumbai, India. E-mail: ashwininb@yahoo.com 2 Clinical Research Institute, Advanced Centre for Research and Treatment of Cancer, Khargar, Mumbai, India 3 National Institute of Immunohaematology (ICMR), King Edward Memorial Hospital, Parel, Mumbai, India 4 Department of Surgery, Tata Memorial Hospital, Parel, Mumbai, India 5 Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai, India Accepted 16 June 2009 Published online 11 August 2009 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/hed.21211 Abstract: Background. Fanconi’s anemia (FA) is a rare autosomal recessive genetic disorder characterized by congenital anomalies, progressive aplastic anemia, and a predisposition for malignancies. Solid tumors in the head and neck region, especially in the tongue, are rarely observed. Management of these patients is a challenge because of hematological complications and increased toxicities. Methods. We report a case of Fanconi’s anemia in a 27- year-old man with carcinoma of the base of tongue (T2N0M0) who was treated with radical radiation therapy to a dose of 70 Gy/35 fractions/51 days. We have also done in vitro radiosensitivity tests. Results. The patient tolerated the radiation treatment well and completed it without any interruptions. In vitro studies did not show any increased radiosensitivity in this patient. Conclusion. Head and neck cancer in a patient with FA requires individualized treatment. The decision about opting for different modalities should be based on a balanced Correspondence to: A. Budrukkar VC 2009 Wiley Periodicals, Inc. approach with respect to locoregional control and toxicities of the treatment. VC 2009 Wiley Periodicals, Inc. Head Neck 32: 1422–1427, 2010 Keywords: Fanconi’s anemia; base of tongue; radiation therapy; head and neck cancer; radiosensitivity Fanconi’s anemia (FA) is a rare autosomal recessive genetic disorder characterized by congenital anomalies, progressive aplastic anemia leading to pancytopenia, and a predisposition for malignancies. 1 Congenital anomalies in FA clinically manifest as skeletal, renal, ophthalmological malformations, and chromosomal aberrations. The disease involves multiple organs that include skin, genitourinary, musculoskeletal, renal, and neurological systems. The clinical findings in FA patients are abnormal skin pigmentation like café au lait spots, abnormal male gonads (absent, atrophic, or abnormal 1422 RT for Base of Tongue SCC in Fanconi’s Anemia HEAD & NECK—DOI 10.1002/hed October 2010
testis, hypospadias, undescended testis), microcephaly, short stature, hypoplastic thumb with or without radial anomalies, renal defects, and developmental delay, mental retardation, and learning disability. 2,3 FA is associated with increased risk of malignancies, and the risk further increases with bone marrow transplantation, which is done for treatment of hemopoietic failure associated with the disease. 4,5 The cause of development of cancer in FA is thought to be attributable to a defect in maintaining the genome integrity, leading to increased chromosomal instability with defective DNA repair mechanism. 6–8 Although hematological malignancies are 1 of the most common cancers, solid tumors in the head and neck region, especially in the tongue, are also observed. 9–11 Management of cancers in the head and neck region in patients with FA is challenging. Surgery, although considered as an optimal treatment, has its limitations as a result of low counts, risk of infection, and wound-healing issues. 9,12 Radiation therapy or chemotherapy is associated with increased risk of toxicity in these patients because of defective DNA repair mechanism. 9,13,14 There have been instances of variable clinical radiosensitivity and fulminant radiation toxicities even with low doses of radiation. 13–15 Therefore, in vitro sensitivity studies, although not common, have been performed on fibroblast cells or peripheral blood mononuclear cells to predict the in vivo radiation sensitivity. 15,16 We report a case of a young man with FA who was diagnosed with carcinoma of the base of tongue and was treated with radical radiation therapy. We also report the results of an in vitro test for radiosensitivity in our patient and review the literature for FA patients with head and neck cancer. CASE REPORT A 27-year-old man was referred to our hospital for evaluation of a base-of-tongue lesion that had appeared 3 months earlier. Oral examination revealed a well-circumscribed, ulceroproliferative lesion on the left side of the base of tongue measuring 2.5 cm in diameter. Neck examination showed no cervical lymphadenopathy. On general physical examination, he was physically retarded (short stature, microcephaly, and microophthalmia) with atrophic testis and a few FIGURE 1. (A and B) Axial and sagittal MR images of the patient with Fanconi’s anemia show mass on the base of tongue (left > right). café au lait spots on skin, particularly of the lower extremities. MRI showed a well-localized soft tissue mass on the base of tongue (left > right), with no significant cervical lymphadenopathy (Figures 1A and 1B). The histopathology review showed squamous cell carcinoma. Therefore, a diagnosis of carcinoma of the base of tongue, T2N0M0 (stage II), was made. The complete blood count, showed features of generalized pancytopenia (total leukocyte count, 1.8 10 9 /L; hemoglobin, 7.1 gm/dL; and platelets, 17 10 9 ). Complete blood count was repeated but pancytopenia persisted. The patient underwent a bone marrow aspiration and biopsy, which revealed hypocellular marrow. In view of his abnormal morphological features and unexplained hypocellular marrow, the patient was advised for chromosomal studies. Subsequently, chromosomal breakage analysis was done in peripheral blood lymphocytes in the presence of DNA crosslinking agents, diepoxybutane (DEB) and mitomycin C (MMC), which revealed a high frequency of chromosomal breakage (6.2 RT for Base of Tongue SCC in Fanconi’s Anemia HEAD & NECK—DOI 10.1002/hed October 2010 1423
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Genotype-Molecular Phenotype Correl
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CONTENTS Page No Synopsis 1 List of
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Synopsis
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Synopsis Genotype-Molecular Phenoty
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Synopsis Materials and Methods: 1.
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Synopsis loading control. PCR produ
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Synopsis 7.1 Percent cell death aft
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Synopsis slides were then dried and
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Synopsis range 41.77% - 90.95% at 5
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Synopsis 5. Genotyping of genes: Ge
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Synopsis G2/M arrest and delaying e
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Synopsis may have an important bear
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Synopsis References: 1. Bobba, R.;
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Abbreviations MOPS : 3-(N-morpholin
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List of Figures Fig. 28: Percent re
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Chapter 1 Introduction
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Introduction In previous studies fr
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Introduction important carcinogenes
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Review of Literature The yet undeci
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Review of Literature Fig. 2: Incide
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Review of Literature sustained angi
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Review of Literature 2.6 Genotype p
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Review of Literature 2.7.2 Biologic
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Review of Literature Table 1: Steps
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Review of Literature future analysi
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Review of Literature Inefficient ce
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Review of Literature XRCC1 (X-ray r
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Review of Literature 2.9.2 Gene inv
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Review of Literature MPO gene polym
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Review of Literature important role
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Materials and Methods Source of che
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Materials and Methods Method: EBV-t
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Materials and Methods Immunophenoty
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Materials and Methods with 500 μl
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Materials and Methods cDNA it can b
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Materials and Methods Cobalt-60 iso
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Materials and Methods specific bind
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Materials and Methods h half of the
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Materials and Methods phenol and th
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Materials and Methods 7. Filter ste
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Materials and Methods viz. EXO-SAP
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Materials and Methods Table 2: List
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Materials and Methods SMAD6 AREG HM
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Materials and Methods 3.9 Effect of
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Materials and Methods fresh eppendo
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Materials and Methods Power SYBR Gr
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Results Objective 1 To generate EBV
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Results Fig. 8: Frequency of second
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Results Table 6: Demographics of he
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Results Fig. 10: Cell population do
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Results Fig. 12: Cell surface marke
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Results 4.1.5 Expression of ATM gen
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Results Objective 2 To compare the
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Results Fig. 17: Standardization of
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Results Fig. 19: Standardisation of
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Results The cells were incubated fu
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Results 4.2.3.1 Percent G2 delay af
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Results 4.2.3.2 Effect of BPDE expo
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Results Fig. 29: Comparison of perc
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Results Fig. 31: Percent cell death
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Results normalization with baseline
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Results 4.2.5.2 Real time PCR valid
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Results homozygous wild-type, heter
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Results Fig. 36b: Electrophoresis o
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Results Fig. 37a: Representative el
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Page 158 and 159: Chapter 6 Summary and Conclusions
Page 160 and 161: Summary and Conclusions Statistical
Page 162 and 163: Bibliography 1. Dikshit, R.; Gupta,
Page 164 and 165: Bibliography 43. Lei, D.; Sturgis,
Page 166 and 167: Bibliography 76. Fry, R. C.; Svenss
Page 168 and 169: Bibliography 115. Kote-Jarai, Z.; M
Page 170 and 171: Bibliography 149. Hashibe, M.; Bren
Page 172 and 173: Bibliography 183. Bergamaschi, D.;
Page 174 and 175: Bibliography 216. Bondy, M. L.; Wan
Page 176 and 177: Indian J Med Res 135, June 2012, pp
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Page 188 and 189: FIGURE 2. Chromosomal breakage anal
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