Aim: Thiamine‐responsive megaloblastic anaemia syndrome (TRMA) is the association of diabetes mellitus, anaemia and deafness, due to mutations in SLC19A2, encoding a thiamine transporter protein. This is a unique monogenic form of vitamin‐dependent diabetes for which there is limited long‐term data. We aimed to study genotype–phenotype relationships and long‐term follow‐up in our cohort. Methods: We have studied 13 patients from seven families and have follow‐up data for a median of 9 y (2–30 y). Results: All patients originated from Kashmir or Punjab, and presented with non‐immune, insulin‐deficient diabetes mellitus, sensorineural deafness and a variable anaemia in the first 5 y of life, the anaemia progressing to megaloblastic and sideroblastic changes in the bone marrow. The anaemia and diabetes mellitus responded to oral thiamine hydrochloride 25 mg/d, but during puberty thiamine supplements became ineffective, and almost all patients require insulin therapy and regular blood transfusions in adulthood. All patients are homozygous for mutations in the SLC19A2 gene. We have identified a novel missense mutation (T158R) that was excluded in 100 control alleles. Conclusion: Diabetes in this syndrome is due to an insulin insufficiency that initially responds to thiamine supplements; however, most patients become fully insulin dependent after puberty. A mutation screening strategy is feasible and likely to identify mutations in almost all cases.

Diabetes in this syndrome is due to an insulin insufficiency that initially responds to thiamine supplements; however, most patients become fully insulin dependent after puberty. A mutation screening strategy is feasible and likely to identify mutations in almost all cases.

Background and purpose: 3-dimensional conformal therapy (3DCRT) is widely employed radiation therapy technique for breast cancer, but there is still need to minimize the doses to organ at risk (OAR) using 3DCRT. A few clinical studies have discussed using intensity modulated radiation therapy (IMRT) to address this shortfall. Simultaneous integrated boost (SIB) has been used in head and neck and prostate cancer, and there is a growing interest in using SIB for breast cancer too. This study aimed to compare SIB-IMRT versus SIB-3DCRT for breast cancer patients. Materials and Methods: SIB-3DCRT treatment plans were created for 36 consecutive patients. Dose was prescribed as 45 Gy in 25 fractions to the planning target volume (PTV)-1 and 60 Gy in 25 fractions to PTV-2. Treatment plans were normalized to 95% of PTV volume receiving 95% of the prescription dose. The conformity index (CI), homogeneity index (HI), lung dose, heart dose, left anterior descending artery(LAD) dose, and low dose volume and integral dose of normal healthy tissue were recorded and analyzed. Results: With the use of IMRT technique, there was an improvement in CI (0.14) when compared to CI of 3DCRT (0.18; p = 0.01). However, there was no significant difference in the HI (p = 0.45). On average, the V20Gy of ipsilateral lung was 37.9 % for 3DCRT and 22.4 % (p < 0.01) for IMRT, whereas the V20Gy of total lung (ipsilateral + contralateral) was 21.8% for 3DCRT and 12.14 (p < 0.01) for IMRT. Similarly, average V40Gy of heart was 7.5 % for 3DCRT and 2.13 % (p = 0.01) for IMRT. The LAD maximum dose to left side breast patients, on average, was 39.5 Gy for 3DCRT and 29.17 Gy (p = 0.03) for IMRT. The average number of monitor units was about 180 for 3DCRT and 1441 (p < 0.01) for IMRT. Conclusion: IMRT for breast cancer treatment is feasible. In comparison to 3DCRT, IMRT can reduce the maximum dose to the target volume, and dose to the OAR. However, 3DCRT technique is superior in terms of low dose volume, integral dose, and treatment time. With the use of breath-hold gated technique in IMRT, it can further improve the target coverage and reduction of doses to the heart, lung, and LAD. SIB technique could reduce the overall treatment duration by about one week.

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