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Every year more and more innovative pharmacological agents are introduced medicine, to treat systemic diseases. Due to these rapid and recent advancements, many patients are receiving treatment with a high variety of drugs, such as selective serotonin reuptake inhibitors, bisphosphonates, tumor necrosis factor (TNF)-α inhibitors, cyclosporine, and steroids. Since implant and osseous surgery are common treatment modalities used, within dentistry, it is of critical important to acknowledge and discuss the potential effects of selective serotonin reuptake inhibitors, bisphosphonates, TNF-α inhibitors, cyclosporine, and steroids, on bone healing. The present paper discusses the possible detrimental ramifications and risks these drug classes may have on bone healing., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Radiotherapy is essential in the treatment of locally advanced rectal cancer. Side effects of radiotherapy in the treatment of rectal cancer have a great effect on quality of life. The aim of this retrospective study is to evaluate the correlation between dosimetric parameters and acute toxicity in rectal cancer patients., Methods: We analyzed the Dose Volume Histogram parameters for both the target structures and the Organs at risk of 89 patients. A dedicated statistical analysis was performed for all the acute toxicities showing a frequency rate higher than 20%. A linear logistic regression model was elaborated using the variable showing the highest level of significance at the univariate analysis., Results: The occurrence of proctitis was significantly correlated with three dosimetric parameters: D98% of low ano-rectum, D 98% and D mean of low ano-rectum wall. A predictive linear logistic regression model reports that the D 98% of the wall of the low ano-rectum must be < 38.5 Gy to decrease the rate of proctitis. A general analysis on grade 2 acute toxicity occurrence reported that it was correlated with D98% of low ano rectum., Conclusions: Two dose constraints were elaborated: D98%<33.5 Gy for low ano rectum to prevent grade 2 acute toxicity and D98%<25 Gy for low ano-rectum wall to prevent proctitis (grade 1 or superior)., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: Despite the availability of different strategies for ovarian function and/or fertility preservation in young breast cancer patients candidates for chemotherapy, limited data are available on patients' actual need of these options., Patients and Methods: The PREFER study is a prospective cohort study including premenopausal women with newly diagnosed early stage breast cancer between the age of 18 and 45 years and candidates for chemotherapy. The study aimed to investigate patients' preferences and their choices of the different available strategies for ovarian function and/or fertility preservation (i.e. acceptance rate) and reasons for refusal., Results: A total of 131 consecutive patients referred from a single breast unit were included. Median age was 38.9 years with 92 patients (70.3%) diagnosed at ≤ 40 years. The majority of patients (122, 93.1%) were concerned about the risk of treatment-induced premature ovarian insufficiency (POI) and/or infertility. A total of 120 (91.6%) patients underwent temporary ovarian suppression with gonadotropin-releasing hormone agonists during chemotherapy for ovarian function preservation. Among patients with ≤40 years, only 11 (12.0%) decided to access cryopreservation strategies for fertility preservation. The main reason for not accessing the fertility unit was completion of family planning before breast cancer diagnosis; for patients who accessed the fertility unit, fear of the procedure was the main reason to refuse the proposed cryopreservation strategies., Conclusion: Despite the majority of young breast cancer patients are concerned about the risk of treatment-induced POI and/or infertility, only a limited number of them required to access the fertility unit to undergo cryopreservation strategies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction Although hormonal-therapy is the preferred first-line treatment for hormone-responsive, HER2 negative metastatic breast cancer, no data from clinical trials support the choice between hormonal-therapy and chemotherapy.Methods Patients were divided into two groups according to the treatment: chemotherapy or hormonal-therapy. Outcomes in terms of clinical benefit and median overall survival (OS) were retrospectively evaluated in the two groups. To calculate the time spent in chemotherapy with respect to OS in the two groups, the proportion of patients in chemotherapy relative to those present in either group was computed at every day from the start of therapy.Results From 1999 to 2013, 119 patients received first-line hormonal-therapy (HT-first group) and 100 first-line chemotherapy (CT-first group). Patients in the CT-first group were younger and with poorer prognostic factors as compared to those in HT-first group. Clinical benefit (77 vs 81%) and median OS (50.7 vs 51.1 months) were similar in the two groups. Time spent in chemotherapy was significantly longer during the first 3 years in CT-first group (54-34%) as compared to the HT-first group (11-18%). This difference decreased after the third year and overall was 28% in the CT-first group and 18% in the HT-first group.Conclusions The sequence first-line chemotherapy followed by hormonal-therapy, as compared with the opposite sequence, is associated with a longer time of OS spent in chemotherapy. However, despite the poorer prognostic factors, patients in the CT-first group had a superimposable OS than those in the HT-first group.

Introduction: Endocrine therapy is considered the cornerstone treatment for postmenopausal women with hormone-receptor positive metastatic breast cancer. Fulvestrant is a selective estrogen receptor down-regulator (SERD) with demonstrated activity and efficacy in the treatment of these patients., Areas Covered: The present manuscript aims to review the mechanism of action of fulvestrant, the clinical efficacy data with the use of different dosages and schedules, and finally its role in association with other medications. Expert commentary: Fulvestrant is an active compound with an excellent safety profile for the treatment of women with hormone receptor-positive metastatic breast cancer, The combination of fulvestrant with targeted agents showed increased efficacy and is expected to become a new standard treatment. Results of two clinical trials (i.e. the FALCON and FEVEX trials) are awaited to better clarify the place of fulvestrant in the armamentarium of the available therapies for the treatment of hormone receptor-positive metastatic breast cancer.

Introduction: Breast cancer in young women represents a public health problem with specific age-related issues to be faced by both patients and their treating physicians., Areas Covered: This manuscript reviews the recent data on the medical management of young women with early-stage HER2-negative breast cancer., Expert Opinion: For women candidates to receive (neo)adjuvant chemotherapy, anthracycline- and taxane-based regimens are standard of care. In high-risk patients, dose-dense regimens should be preferred; in women with triple-negative breast cancer and BRCA mutations, the addition of platinum compounds may also be considered. Several adjuvant endocrine therapy options have become available for the treatment of premenopausal women with early-stage luminal breast cancer. Specifically, young patients at low risk of relapse may be safely spared chemotherapy: endocrine therapy alone with tamoxifen for 5 years is the most appropriate treatment. In women at higher risk of relapse, ovarian function suppression is therapeutic: in this scenario, luteinizing hormone-releasing hormone agonists (LHRHa) should be considered in addition to tamoxifen or aromatase inhibitors. To women concerned about the possible risk of chemotherapy-induced premature ovarian failure, the use of temporary ovarian suppression with LHRHa should be proposed as a valid strategy to potentially preserve ovarian function and fertility.

The aim of the study is to evaluate the efficacy and safety of a three-drug chemotherapy regimen including gemcitabine, carboplatin, and paclitaxel as induction therapy in clinical stage III non-small cell lung cancer (NSCLC). Patients aged 18-75 years, ECOG PS 0-1, with unresectable clinical stage IIIA or IIIB NSCLC suitable for definitive radiation treatment, were treated in a phase II study with i.v. carboplatin AUC 5 and i.v., paclitaxel 175 mg/m(2) on day 1, and i.v. gemcitabine 800 mg/m(2) on days 1 and 8, every 3 weeks for 3 cycles, as previously assessed in a dose-finding study. Primary end point was overall response rate (ORR). Secondary end points included: toxicity, progression-free survival (PFS), resection rate, and overall survival (OS). Out of the 60 enrolled patients, 49 were males and 11 females, 31 patients had stage IIIA and 29 stage IIIB NSCLC. Forty-four partial responses and one complete response were observed, for an ORR of 75 %. The most frequent G3-G4 toxicity included: neutropenia (in 23 % of cases), hypertransaminasemia (12 %), and diarrhea (5 %). With a median follow-up of 15 months (range 2-72), median PFS was 10.5 months (95 % CI 9.9-11.4) and median OS was 21.1 months (95 % CI 19.7-22.8). Fourteen stage IIIA patients underwent surgery, for a resection rate of 45 %. A median PFS of 17.8 months (95 % CI 16.2-19.7) and a median OS of 25.5 months (95 % CI 23.0-28.4) were observed in stage IIIA patients. The three-drug chemotherapy regimen, at the employed dose, demonstrated a considerable disease response and resection rate, with acceptable toxicity.

Breast cancer is the most frequent tumor among women worldwide and is the second cause of cancer-related mortality in the US. Metastatic breast cancer (MBC) accounts for less than 10% of newly diagnosed breast cancer patients and about 30% of early breast cancer patients will develop recurrent, advanced, or metastatic disease. It remains an incurable illness and the primary goal of its management is palliative. Several agents are active for the first-line treatment of MBC. The taxanes, paclitaxel and docetaxel, represent the standard of care for the treatment of these patients. Among the various schedules, docetaxel can be administered weekly, achieving similar efficacy results with lower toxicity compared with conventional schedules. Weekly docetaxel (25-40 mg/m(2)) has been widely tested in several phase I and II studies both as a single agent and in multichemotherapy regimens, reaching overall response rates ranging from 26% and 86% or 20% and 73% with docetaxel alone or in combination, respectively, depending on doses, associations, and line of treatment. Overall, published data support the administration of weekly docetaxel for the treatment of MBC patients even if data from phase III randomized trials are still lacking.

Background: : To date, the standard treatment for patients who have carcinoma of unknown primary site has not been established., Methods: : In this randomized Phase II study, 66 previously untreated patients (33 patients per arm) with carcinomas of unknown primary site received cisplatin (35 mg/m2) and gemcitabine (1000 mg/m2) with either paclitaxel (70 mg/m2) or vinorelbine (25 mg/m2), and all drugs were administered intravenously on Days 1 and 8 of a 21-day cycle. Twenty-nine patients (44%) presented with > or =2 involved sites. The pathologic diagnosis was mainly adenocarcinoma (48 patients; 72.7%) and squamous carcinoma (7 patients; 10.6%)., Results: : In the first arm, 16 patients (48.5%) experienced an objective response, and 9 patients (27.2%) had disease stabilization. In the vinorelbine-containing arm, 14 patients (42.3%) experienced an objective response, and 8 patients (24.2%) had disease stabilization. The median response duration and the median time to progression were similar in both treatment arms; the median overall survival was 9.6 months (95% confidence interval, 7.11-12.09 months) for patients who received the cisplatin/gemcitabine/paclitaxel regimen and 13.6 months (95% confidence interval, 6.61-20.59 months) for patients who received the vinorelbine combination. Grade 3 and 4 toxicities were more frequent in the paclitaxel-containing arm., Conclusions: : Both combinations satisfied the 2-step design, demonstrating antitumor activity without relevant differences in response rates or response duration; however, the vinorelbine-containing regimen yielded superior results both in terms of overall survival (13.6 months vs 9.6 months) and in terms of treatment tolerability. Therefore, according to a pick the winner attitude, the combination of cisplatin/gemcitabine/vinorelbine may be considered in the design of future randomized, Phase III trials for patients with carcinomas of unknown primary site., (Copyright 2006 American Cancer Society.)

It is well established that cancer arises in chronically inflamed tissue, and this is particularly notable in the gastrointestinal tract. Classic examples include Helicobacter pylori-associated gastric cancer, hepatocellular carcinoma, and inflammatory bowel disease-associated colorectal cancer. Growing evidence suggests that these associations might be not casual findings. Focusing on individual cytokines has generated evidence that anti-inflammatory cytokine interleukin (IL)-10 and transforming growth factor-beta1 (TGF-beta1) may have a complex role in gastrointestinal carcinogenesis. As an example, IL-10-deficient mice develop severe atrophic gastritis and a chronic enterocolitis, developing colorectal cancer similar to human inflammatory bowel disease-associated neoplasia. TGF-beta1 is a multifunctional signaling molecule with a wide array of roles. Animal experiments suggest that TGF-beta1 plays a biphasic role in carcinogenesis by protecting against the early formation of benign epithelial growths, but promoting a significant stimulation of tumor growth invasion and metastasis during tumor progression. We assessed association of functional polymorphisms (-1082G/A; -592C/A) and TGF-beta1 (-509C/T; +869C/T) influencing the IL-10 production to colorectal cancer risk in a case-control study of 62 patients and 124 matched controls. No significant differences were observed among cancer patients and controls for IL-10 -1082G/A; -592C/A genotype frequencies. Evaluation of odds ratios (OR) for the TGF-beta1 +869C/T genotypes showed a significant increased risk for individuals bearing +869CC genotype compared to +869CT- and +869TT-positive individuals. These results suggest that the +869C allele, responsible for a Leu-->Pro substitution in the signal peptide sequence of the TGF-beta1 protein, may have a predisposing role in the development of colorectal cancer.