Oral Complications of Head and Neck Cancer Therapy

Current therapies for Head and Neck cancer treatment are extremely advanced. Though, they cause oral complications which have deleterious effects on basic life functions, affect oral and overall health, may lead to significant morbidity and treatment discontinuation and have an impact on survivorship and quality of life. As new therapies are introduced, a new spectrum of oral complications is rising, compromising the mucosal integrity and the salivary function, that may not be recognized, reported and treated properly. Oral complications, often permanent and extremely painful, may include mucositis, xerostomia, dysgeusia, infections, trismus and fibrosis, risk of dental disease and necrosis of the jaw, neurosensory disorders and when targeted therapies and immunotherapy are involved, aphthoid and lichenoid lesions can also be reported. Increased awareness is required for the prevention and management of these complications, which can be best provided by a multidisciplinary team.

Pancreatic malignancy in the backdrop of chronic pancreatitis: How much to push the boundaries to achieve R0 resection

Tumors of the body and tail of the pancreas are often more aggressive than tumors of the head and would have often undergone metastatic spread to other organs at the time of diagnosis. Most patients with carcinoma of the body and tail of the pancreas present at a late stage. Surgery is only indicated in those patients in whom there is no evidence of metastatic spread. Surgery is often not possible in cancers of the body and tail of the pancreas if the tumor invades celiac artery. Controversy exists regarding the margin status impact of microscopic resection margin involvement (R1) after pancreaticoduodenectomy (PD) for PDAC. There are reports indicating the rate of R1 resections increases significantly after PD if pathological examination is standardized. In this report, we present the case of a 56-year-old female who had undergone lateral pancreaticojejunostomy for chronic pancreatitis 8 years ago, but has now developed malignancy of the body and tail of the pancreas involving multiple organs. This patient underwent en bloc resection involving: 1. distal pancreatectomy with jejunal loop (lateral pancreaticojejunostomy) resection; 2. splenectomy; 3. left nephrectomy; 4. total gastrectomy; and 5. segmental colectomy with reconstruction by esophagojejunostomy, jejunojejunostomy, and colocolic anastomosis. The infrequent occurrence of tumor in the distal gland and advanced tumor stage at the time of diagnosis have both combined to produce therapeutic nihilism/dilemma in the minds of many surgeons. This report highlights the decision on how much to the push limits for multi-organ resection (en bloc resection with distal pancreatectomy, gastrectomy, splenectomy, colectomy, nephrectomy) with the intent of achieving R0 status in spite of the complexity of surgery in selected patients.

The evolving role of PARP inhibitors in advanced ovarian cancer

The field of ovarian cancer has been revolutionized with the use of poly (ADP-ribose) polymerase (PARP) inhibitors, which present greater inhibition effect in epithelial subtype due to high rates of homologous recombination deficiency. PARP inhibition exploits this cancer pitfall by disrupting DNA repair, leading to genomic instability and apoptosis. Three PARP inhibitors (olaparib, niraparib, and rucaparib) are now approved for use in women with epithelial ovarian cancer, while others are under development. Among women with BRCA1/2 mutations, maintenance PARP therapy has led to a nearly fourfold prolongation of PFS, while those without BRCA1/2 mutations experience an approximately twofold increase in PFS. Differences in trial design, patient selection and primary analysis population affect the conclusions on PARP inhibitors. Limited OS data have been published and there is also limited experience regarding long-term safety. With regard to toxicity profile, there are no differences in serious adverse events between the experimental and control groups. However, combining adverse event data from maintenance phases, a trend towards more events in the experimental group, compared with controls, has been shown. The mechanisms of PARP-inhibitor resistance include restoration of HR through reversion mutations in HR genes, leading to resumed HR function. Other mechanisms that sustain sufficient DNA repair are discussed as well. PARP inhibitors play a pivotal role in the management of ovarian cancer, affecting the future treatment choices. Defining exactly which patients will benefit from them is a challenge and the need for HRD testing to define ‘BRCA-ness’ will add additional costs to treatment.

Prognostic value of cytokines in breast cancer: Correlation with positive hormonal status and obesity

Background The relation of interleukin 6 (IL6) and molecular subtypes as well as body mass index is not well settled. Little is known about interferon gamma (IFγ) and prognosis of breast cancer. Patient and methods Serum level of IL6 and IFγ was assessed by enzyme-linked immunosorbent assay (ELISA) and correlated with the TNM staging, molecular subtypes, and body mass index. Results Among 78 patients, the median age was 54 years. The majority of the cases were T2 (62.8%), N1 (38.5%), and M0 (89.74%) with stage II being the most common (47.4%). Most females were estrogen receptor (97.9%) and progesterone receptor positive (96.9%) with high Ki67 ≥ 20 (61.5%). Her2 neu positive presented 16.7%. Luminal A and luminal B presented 29.5% and 53.8%, respectively. Obese patients presented by far the majority (82.1%). The median level of IL6 and IFγ was 56.20 ± 28.715 and 76.37 ± 41.54, respectively. IL6 was significantly correlated with tumor size (P = 0.001), nodal involvement (P = >0.0001), the presence of metastasis (P = 0.008), and the stage (P = >0.0001). High level of IL6 was associated with positive estrogen receptor, Her2 neu positive, luminal A, and being obese (P = 0.09, 0.07, 0.06, and 0.05, respectively). High IFγ was only associated with lower nodal burden being significantly higher in N1 than in N3 (118.15 ± 31.07 vs 76.37 ± 44.46, P = 0.01) and early stage (P = 0.02). Conclusion IL6 level was correlated to the initial staging, hormonal status, being Her2 positive, and obesity. The IFγ level was inversely correlated IL6 regarding the nodal status (P = 0.05).

Comparative study of low dose of capecitabine versus standard dose in metastatic breast cancer: Efficacy and safety

Background A lower dose of capecitabine revealed better toxicity profiles and comparable efficacy in treatment of metastatic breast cancer (MBC). We aimed to evaluate the efficacy and toxicity of lower dose of capecitabine in comparison with the standard dose. Patients and methods Patients were enrolled in two groups. Group 1 included 21 patients who received the standard dose of capecitabine (1250 mg/m2 twice daily [BID] for 14 days), while the patients in group 2 (19 patients) received lower dose of capecitabine (850 mg/m2 BID for 14 days) every 3 weeks. Results In group 1, dose reduction was reported in 12 (57.1%) patients versus 1 patient in group 2 (5.3%; P = 0.0005). Patients in group 1 reported higher toxicity rates without any significant difference between the groups. The median duration of response was 17 weeks in group 1, while it was 19 weeks in group 2. Disease progression was recorded in 10 (47.6%) patients in group 1 versus 8 (42.1%) patients in group 2 (P = 0.81). The mean time to progression was 8.16 ± 0.63 months and the median was 10.1 months in group 1, while the mean was 8.98 ± 0.75 months and the median was 10 months in group 2 (P = 0.66). The overall survival had a mean of 11.94 ± 0.754 and 11.24 ± 0.665 months, while the median was 13.1 and 13 months in groups 1 and 2, respectively (P = 0.9). Conclusion A lower dose of capecitabine provides MBC patients with an active therapy that can be continued for prolonged periods to achieve long-term disease control without compromising its antitumor activity.

Antidiabetic drugs and the risk of cancer: beneficial, neutral, or detrimental?

The prevalence of diabetes mellitus is rapidly rising, especially in low- and middle-income countries. Also, early-onset diabetes is on the rise, and millions of individuals have to be on antidiabetic medications for a prolonged period. Therefore, more people are getting exposed to the adverse effects of antidiabetic medications. Cancer is among the top ranking causes of death worldwide. Researches are still ongoing to understand the etiologies, precipitants, risk factors, correlates, and predictors of cancers. Diabetes mellitus is associated with various cancers, as extensively documented in the literature. There are conflicting reports about the association between antidiabetic drugs and cancer. This is even of crucial importance, considering that the prevalence of diabetes is rising. Insulin glargine is reported to be associated with cancers, but clinical trials have not confirmed this. Metformin is largely believed to be beneficial in oncologic practice. Glibenclamide is reported to reduce tumor growth. The association between pioglitazone and bladder cancer is still an area for further research. Meglitinides have also been associated with cancers. Incretin-based therapy and the α-glucosidase inhibitors appear to have beneficial effects on cancers. There is still a need for randomized multicentric clinical trials to further substantiate and clarify reports from epidemiological studies. Further in vitro studies will also be necessary to characterize the interaction of these pharmacological agents with other molecules in the body.

Impact of vitamin D serum levels on clinicopathological features and outcome in advanced pancreatic carcinoma

Background Growing evidence encourages the preventive role of vitamin D in pancreatic carcinoma (PC). Meanwhile, the prognostic or predictive role needs more investigations. This study aimed to evaluate the correlation between serum vitamin D levels and the clinicopathological features with the outcome in advanced pancreatic carcinoma (APC). Materials and methods The current prospective study included 176 patients with APC. Assessing 25-hydroxy vitamin D is the most accurate method to measure the serum vitamin D levels. Serum vitamin D levels <20 ng/ml are defined as vitamin D deficiency, while levels ranging from 20 to 29 ng/ml are defined as vitamin D insufficiency. Before any treatment modalities were administered, the serum vitamin D levels were measured by enzyme-linked immunosorbent assay (ELISA). Results Serum vitamin D insufficiency and deficiency were detected in 28.4% and 31.8%, respectively. A large tumor size, higher grade, liver metastasis, higher serum level of CA 19-9, poor ECOG PS, and low overall response rate (ORR) were associated with lower serum vitamin D levels (p = 0.000). The median follow-up period was 7.6 months (range 0.6–18.6). The ORR was 23.2%, 54%, and 82.9% of vitamin D deficiency, insufficiency, and normal levels of vitamin D, respectively. The median OS was 11.4 months for patients with normal serum vitamin D levels, compared with 2.7 and 7.03 months for serum vitamin D deficiency and insufficiency, respectively. Conclusion Among patients with APC, serum vitamin D levels are considered a promising prognostic factor. It is associated with various poor prognostic features and worse survival outcome.

Concordance Between ER, PR, HER2 neu Receptors Before and After Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

Background Introducing neoadjuvant chemotherapy (NCT) in a breast cancer patient may be associated with changes in estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth hormone receptor 2 (HER2) status. Method In our prospective cohort study, we evaluated the impact of change in estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth hormone receptor 2 (HER2) on the prognosis of breast cancer patients treated with neoadjuvant chemotherapy (NCT). We investigated 110 patients with locally advanced breast cancer for ER, PR and HER2 status of their lesions before and after NCT. Result For hormone receptor status (HR) (which include ER, PR) of the residual tumor of the patients after receiving NCT, 12 (10.9%) of them changed from HR (+) to HR (−) and 15 (13.6%) changed from HR (−) to HR (+). For HER2 status after NCT, 8 (7.3%) patients changed from HER2 (+) to HER2 (−) and 9 (8.2%) patients changed from HER2 (−) to HER2 (+). Triple negative (TN) tumor phenotype changes occurred in 17 (15.5%) patients. Patients for whom the HR status changed from positive to negative had poor prognosis for both disease-free survival (DFS) and overall survival (OS) in univariate survival analysis. Conclusion Changes in ER, PR, HER2 status and tumor phenotype in breast cancer patients after NCT had a negative prognostic impact and were associated with a poor prognosis.

Interactive role of breast cancer on dyslipidemia and hypertension metabolic risk according to treatment exposure and menopausal status

Background Breast cancer (BC) is the principal cause of cancer related deaths among women worldwide. The available evidence suggests that cardio-metabolic risk factors such as dyslipidemia and hypertension may contribute differently to breast cancer severity and pathogenesis. The aim of this study is to evaluate the interactive role of BC on dyslipidemia and HTN risk according to the type of treatment exposure and menopausal status. Method Observational experimental design implemented; permit to include 134 newly-diagnosed patients who were naïve to any type of treatment interventions and 262 recently-diagnosed patients during their first three months of treatments’ exposure including chemotherapy treatments. Patients with breast cancer were evaluated for dyslipidemia and hypertension biomarkers. Results About 5.0% of breast cancer patients had dyslipidemia. The prevalence of increased triglycerides and total cholesterol were more frequent (p < 0.05) in recently-diagnosed group than in newly-diagnosed patients. While 23% of patients had overt hypertension, with higher (p < 0.05) prevalence in chemo group (28%), triglycerides was higher (p < 0.05) in postmenopausal than premenopausal BC patients (221.0 ± 5.9 vs. 195 ± 4.7 mg/dl). Similarly, the prevalence of abnormal systolic blood pressure (9% vs. 5%) and diastolic blood pressure (11% vs. 7%) was higher (p < 0.05) in postmenopausal patients. Conclusion Dyslipidemia and hypertension biomarkers were prevalent among breast cancer patients and the risk increased in postmenopausal women and after treatments’ exposure specially chemotherapy. This conclusion requires a closer attention by healthcare professionals in order to improve the outcomes after diagnosis and to enhance treatment exposure regarding postmenopausal women.