Hypofractionated radiotherapy after breast-conserving surgery: Clinical and dosimetric factors predictive of acute skin toxicity.

PURPOSE: The purpose of this study was to evaluate acute skin toxicity in early breast cancer patients treated with hypofractionated radiotherapy (HFRT) after breast-conserving surgery and to identify factors predictive for grade ≥ 2 acute skin toxicity. MATERIALS AND METHODS: A monocentric retrospective study was carried out using cases treated between December 2017 and November 2020. We analyzed data from 202 patients with early breast cancer treated with 3D hypofractionated RT (40.05 Gy in 15 fractions) to the whole breast with or without regional lymph nodes, followed by 13.35 Gy in 5 fractions to the tumor bed. Acute skin toxicity was monitored during RT according to CTCAE (common toxicity criteria for adverse events) scale. Univariate and multivariate analyses were performed to assess predictive factors of acute skin toxicity. RESULTS: Overall, there was no erythema in 9%, grade 1 erythema in 64.5%, grade 2 in 24%, and grade 3 in 2.5%. No grade 4 erythema was seen. Median delay between RT initiating and maximum skin reaction was 22 days (range 4-44 days). No patient interrupted treatment. In univariate analysis, the rate of acute skin toxicity grade 2---3 (G2-3) was significantly higher for patients with larger tumor size (p = 0.02), body mass index > 27 (p = 0.04), and time between chemotherapy (CT) and RT less than 20 days (p = 0.01). Dosimetric risk factors for acute skin toxicity G2­3 were breast volume > 800 cc (p = 0.000), boost volume > 18 cc (p = 0.002), V105% > 40 cc (p = 0.03), and Dmax > 56 Gy (p = 0.007). CT, trastuzumab, regional lymph node radiation, and age were not correlated with increased skin toxicity. In multivariate analysis, acute skin toxicity correlated with T stage (p = 0.032), breast volume > 800 cc (p = 0.012), boost volume > 18 cc (p = 0.04), and Dmax > 56 Gy (p = 0.035). CONCLUSION: Our results confirm that whole breast with or without lymph nodes hypofractionated RT is safe and well tolerated. The factors strongly associated with a decreased risk of G2­3 skin toxicity are T1, breast volume < 800 c, boost volume < 18 cc, and Dmax < 56 Gy. Long-term follow-up is needed to evaluate late toxicity.

Development of a custom next-generation sequencing panel for the determination of bladder cancer risk in a Tunisian cohort.

BACKGOUND: Bladder cancer (BCa) is a heterogeneous disease caused by the interaction between environmental and genetic risk factors. The goal of this case-control study was to evaluate the implication of a selected SNP panel in the risk of BCa development in a Tunisian cohort. We were also interested in studying the interaction between this predictive panel and environmental risk factors. METHODS: The case/control cohort was composed with 249 BCa cases and 255 controls. The designed Bladder cancer hereditary panel (BCHP) was composed of 139 selected variants. These variants were genotyped by an amplification-based targeted Next-Generation Sequencing (NGS) on the Ion Torrent Proton sequencer (Life Technologies, Ion Torrent technology). RESULTS: We have found that rs162555, rs2228000, rs10936599, rs710521, rs3752645, rs804276, rs4639, rs4881400 and rs288980 were significantly associated with decreased risk of bladder cancer. However the homozygous genotypes for VPS37C (rs7104333, A/A), MPG (rs1013358, C/C) genes or the heterozygous genotype for ARNT gene (rs1889740, rs2228099, rs2256355, rs2864873), GSTA4 (rs17614751) and APOBR/IL27 (rs17855750) were significantly associated with increased risk of bladder cancer development compared to reference group (OR 2.53, 2.34, 1.99, 2.00, 2.00, 1.47, 1.96 and 2.27 respectively). We have also found that non-smokers patients harboring heterozygous genotypes for ARNT/rs2864873 (A > G), ARNT/ rs1889740 (C > T) or GSTA4/rs17614751 (G-A) were respectively at 2.775, 3.069 and 6.608-fold increased risk of Bca development compared to non-smokers controls with wild genotypes. Moreover the ARNT CT (rs1889740), ARNT CG (rs2228099), ARNT TC (rs2864873) and GSS GA genotypes were associated with an increased risk of BCa even in absence of professional risk factors. Finally the decision-tree analysis produced a three major BCa classes. These three classes were essentially characterized by an intensity of tobacco use more than 20 pack years (PY) and the CYP1A2 (rs762551) genotype. CONCLUSIONS: The determined association between environmental factors, genetic variations and the risk of Bca development may provide additional information to urologists that may help them for clinical assessment and treatment decisions. Nevertheless, the underlying mechanisms through which these genes or SNPs affect the clinical behavior of BCas require further studies.

An insight into the diagnostic and prognostic value of HOX A13's expression in non-muscle invasive bladder cancer.

BACKGROUND: Several studies have interrogated the molecular pathways and their interacting genes underlying bladder cancer (BCa) tumorigenesis, yet, the role of homeobox genes is still poorly understood. Specifically, HOXA13, which plays an important role as a major actor in the urogenital tract's development. METHODS: Immunohistochemical (IHC) staining was performed to inspect the differential expression of HOXA13 protein in non-muscle-invasive bladder cancer (NMIBC) and non-tumoral tissues. A semiquantitative scoring system was adopted to evaluate the IHC labeling. Correlation to clinical parameters was performed by descriptive statistics. Overall survival was estimated by the Kaplan-Meier method and Cox regression model. The functional HOX A13 protein association networks (PPI) were obtained using String 11.0 database. RESULTS: HOX A13 exhibited cytoplasmic and nuclear staining. Its expression levels were lower in high-grade NMIBC (HG NMIBC) compared to low-grade ones (LG NMIBC). The expression of HOX A13 was correlated to tumor grade (LG/HG) (p = 0.036) and stage (TA/T1) (p = 0.036). Nevertheless, its expression was not correlated to clinical parameters and was not able to predict the overall survival of patients with HG NMIBC. Finally, PPI analysis revealed that HOX A13 seems to be a part of a molecular network holding mainly PBX1, MEIS, ALDH1A2, HOX A10, and HOX A11. CONCLUSION: The deregulation of HOX A13 is not associated with the prognosis of BCa. It seems to be rather implicated in the early initiation of urothelial tumorigenesis and thus may serve as a diagnostic marker in patients with NMIBC. Further experimentations on larger validation sets are mandatory.

The diagnostic applicability of A-type Lamin in non-muscle invasive bladder cancer.

PURPOSE: Lamin A is a major component of the nuclear lamina maintaining nuclear integrity, regulation of gene expression, cell proliferation, and apoptosis. Its deregulation in cancer has been recently reported to be associated with its prognosis. However, its clinical significance in non-muscle invasive bladder cancer (NMIBC) remains to be defined. MATERIAL/METHODS: Immunohistochemical staining and RT-qPCR were performed to screen the expression patterns of Lamin A/C protein and Lamin A mRNA respectively in 58 high and low grade NMIBC specimens. RESULTS: Lamin A/C protein was expressed only in the nucleus and less exhibited in NMIBC tissues compared to non-tumoral ones. On the other side, Lamin A mRNA was up-regulated in NMIBC compared to controls. Nevertheless, both expression patterns (protein and mRNA) were not correlated to clinical prognosis factors and were not able to predict the overall survival of patients with high-grade NMIBC. CONCLUSIONS: The deregulation of A-type Lamin is not associated with the prognosis of NMIBC, but it could serve as a diagnostic biomarker distinguishing NMIBC patients from healthy subjects suggesting its involvement as an initiator event of tumorigenesis in our cohort.

Uncovering the expression patterns and the clinical significance of miR-182, miR-205, miR-27a and miR-369 in patients with urinary bladder cancer.

BACKGROUND: Given the high recurrence and progression rates and the absence of reliable markers for early detection and prognosis prediction of patients with urothelial bladder cancer (BCa), the exploration of new biomarkers with high specificity is imperative. Mainly, microRNAs (miRNAs), which are involved in the initiation and the progression of BCa. Herein, the expression patterns of miR-182, miR-205, miR-27a and miR-369 were evaluated in patients with urothelial BCa. METHODS AND RESULTS: The expression levels of the miRNAs were investigated in 90 FFPE tissue samples (23 LG NMIBC, 44 HG NMIBC, 23 MIBC) and 10 non tumoral bladder tissues using TaqMan based RT-qPCR. Data analysis was performed using 2-ΔΔCT method. Correlation to clinical characteristics of the patients was performed using descriptive statistics and the receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic value of all miRNAs. MiR-27a, miR-205 and miR-369 were down-regulated whereas miR-182 was up-regulated in patients compared to controls (p < 0.001). MiR-205 and miR-182 positively segregate between NMIBC and MIBC (p = 0.002 and p = 0.000 respectively) whereas the distribution of miR-27a's expression among these tumor groups was almost significant (p = 0.05) and that of miR-369's expression was irrelevant (p = 0.618). Interestingly, miR-182 was discriminative between LG NMIBC and HG NMIBC (p < 0.001) and Ta/T1 tumors (p = 0.000). Furthermore, high levels of miR-182 were potentially predictive of progression in NMIBC patients (p = 0.01). CONCLUSION: Collectively, a selection of miRNAs was found to be aberrantly expressed in BCa suggesting a potential diagnostic value in BCa. In addition, the clinical value of miR-182 and miR-205 as potential prognosis biomarkers was highlighted. Indeed, our data provide additional insights into cancer biology. Further functional or target studies are mandatory to strengthen these findings.

Concurrent Chemoradiotherapy as an Adjuvant Treatment of Primary Central Nervous System Neuroblastoma.

Primary central nervous system neuroblastoma is a rare malignant embryonal tumor. With only few cases reported in the literature, data on regardingthe diagnosis and management of these tumors are limited. We reported a case of primary cerebral neuroblastoma in a 20-year-old woman complaining of progressive headaches. The patient underwent subtotal tumor resection and adjuvant concurrent chemoradiotherapy. The prescription dose was 54 Gy. She remained free of recurrence for 14 months after the end of radiotherapy treatment.

Polymorphisms in NQO1 and MPO genes and risk for bladder cancer in Tunisian population.

BACKGROUND: NAD (P) H: quinone oxidoreductase (1) (NQO1-HGNC: 2874) and myeloperoxidase (MPO-HGNC: 7218) are two enzymes involved in phase II of the xenobiotic metabolism pathway. METHODS: In this study, a case-control analysis was conducted to investigate the relationship between genetic variations in the NQO1 (C609T, rs1800566; IVS1-27 C >G, rs689452) and MPO (G463A, rs2333227) genes and the risk for bladder cancer among Tunisian population. RESULTS: We have found that the MPO 463GA genotype was associated with a decreased risk of developing bladder cancer (p = 0.049; OR = 0.696; 95% CI 0.484-0.999). In contrast, we have found that the NQO1 609CT genotype could increase the risk of bladder cancer patients (p = 0.0039; OR = 1.454; 95% CI = 1.017-2.078). Moreover, patients with "NQO1 609 CT/IVS1-27 CG" genotype show a 2.180-fold increasing risk for developing bladder cancer in comparison to the control group with wild genotype. This OR is estimated at 5.6-fold in smokers patients with "NQO1 609 CT/IVS1-27 CG" genotype. Lastly, study findings suggest that the NQO1 IVS-27 *CG genotype (rs689452) is associated with a risk of progression to muscle invasive bladder cancer. CONCLUSION: Our study suggests that environmental risk factors in association to NQO1 genotypes (NQO1 609 CT/IVS1-27 CG) play an important role in the development of bladder cancer in Tunisian population.

Primary Paratesticular Leiomyosarcoma: A Case Report and Literature Review.

Paratesticular soft tissue sarcomas are very rare malignant mesenchymal tumors. With only few cases reported in the literature, data regarding diagnostic and management of these tumors are limited. We reported a case of primary paratesticular leiomyosarcoma in a 72-year-old man complaining of a progressively growing painless right scrotal mass. The patient underwent radical inguinal right orchiectomy and adjuvant 3D conformal radiotherapy to the tumor bed including the surgical scar. The prescription dose was 54 Gy, and no pelvic irradiation was performed. He remained free of recurrence for the last 16 months.

Cancer care and COVID-19: tailoring recommendations for the African radiation oncology context.

Africa is the second most populous continent after Asia comprising 54 countries. Given the healthcare system deficiencies in Africa, the impact of the COVID-19 pandemic was expected to be disastrous. The first case of COVID-19 on the continent was reported in Egypt on 14 February 2020. By 13 May, cases had been reported in all 54 countries. Several practice guidelines specific to radiation oncology departments have been published, including prioritisation criteria for postponing radiotherapy, continuation of treatment, hypofractionation or even omitting radiotherapy. The oncology community in Africa has suddenly needed to protect both patients and caregivers and to ensure continuity of essential clinical services despite several challenges. Considering equipment unavailability, lack of human resources and poor infrastructure, tailoring COVID-19 pandemic management to the African context seems mandatory and a unified approach to guideline development in this context is encouraged. In this article, we discuss contextual issues coming into play, highlighting steps to be taken by radiotherapy centres in Africa to mitigate fallouts from the current pandemic to ensure the safety of our patients and staff as well as the impact on future care.

Kaposi's sarcoma of the larynx: an unusual location in an HIV-negative patient (a case report).

Head and neck involvement of Kaposi's sarcoma is rarely encountered, especially for the Mediterranean classic subtype. Here we report a case of non-AIDS related laryngeal Kaposi's sarcoma in a 77-year-old Tunisian man complaining of 4-month history of hoarseness and dysphagia. The patient underwent exclusive local radiotherapy with a prescription dose of 45 Gy delivered in 1.8 Gy daily fractions. He remained complaint-free for 3 months.