The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies

Immune checkpoint inhibitors (ICIs) have a modest clinical activity when administered as monotherapy against breast cancer (BC), the most common malignancy in women. Novel combinatorial strategies are currently being investigated to overcome resistance to ICIs and promote antitumor immune responses in a greater proportion of BC patients. Recent studies have shown that the BC abnormal vasculature is associated with immune suppression in patients, and hampers both drug delivery and immune effector cell trafficking to tumor nests. Thus, strategies directed at normalizing (i.e., at remodeling and stabilizing) the immature, abnormal tumor vessels are receiving much attention. In particular, the combination of ICIs with tumor vessel normalizing agents is thought to hold great promise for the treatment of BC patients. Indeed, a compelling body of evidence indicates that the addition of low doses of antiangiogenic drugs to ICIs substantially improves antitumor immunity. In this review, we outline the impact that the reciprocal interactions occurring between tumor angiogenesis and immune cells have on the immune evasion and clinical progression of BC. In addition, we overview preclinical and clinical studies that are presently evaluating the therapeutic effectiveness of combining ICIs with antiangiogenic drugs in BC patients

Clinical care pathway program versus open-access system: a study on appropriateness, quality, and efficiency in the delivery of colonoscopy in the colorectal cancer

Open-access colonoscopy (OAC), whereby the colonoscopy is performed without a prior office visit with a gastroenterologist, is affected by inappropriateness which leads to overprescription and reduced availability of the procedure in case of alarming symptoms. The clinical care pathway (CCP) is a healthcare management tool promoted by national health systems to organize work-up of various morbidities. Recently, we started a CCP dedicated to colorectal cancer (CRC), including a colonoscopy session for CRC diagnosis and prevention. We aimed to evaluate the appropriateness, the quality, and the efficiency in the delivery of colonoscopy with the open-access system and a CCP program in the CRC. Quality indicators for colonoscopy in subjects in the CCP were compared to referrals by general practitioners (OAC) or by non-gastroenterologist physicians (non-gastroenterologist physician colonoscopy, NGPC). Attendance rate to colonoscopy was greater in the CCP group and NGPC group than in the OAC group (99%, 99%, and 86%, respectively). Waiting time in the CCP group was shorter than in the OAC group (3.88 ± 2.27 vs. 32 ± 22.31 weeks, respectively). Appropriateness of colonoscopy prescription was better in the CCP group than in the OAC group (92 vs. 50%, respectively). OAC is affected by the lack of timeliness and low appropriateness of prescription. A CCP reduces the number of inappropriate colonoscopies, especially for post-polypectomy surveillance, and improves the delivery of colonoscopy in patients requiring a fast-track examination. The high rate of inappropriate OAC suggests that this modality of healthcare should be widely reviewed

La radioterapia frazionata stereotattica quale trattamento per i neurinomi del nervo acustico

Scopo dello studio: valutazione dell’efficacia della radioterapia conformazionale stereotassica frazionata (RFS) nel controllo tumorale e nella preservazione della funzionalità dei nervi cranici in pazienti affetti da neurinoma del nervo acustico (NA). Pazienti e Metodi: Da Maggio 1999 a Settembre 2003, 29 pazienti affetti da NA sono stati trattati con RFS. Ventotto hanno ricevuto un dosaggio pari a 50 Gy mentre 1 paziente ha ricevuto soltanto 20 Gy a causa del suo scarso performance status. La mediana della durata del follow up è stata di 23 mesi. Sono stati valutati il controllo tumorale, la preservazione della funzionalità dei nervi cranici e altre tossicità legata al trattamento. Risultati: La percentuale di controllo tumorale è pari al 100% a 3 anni. La preservazione della funzione uditiva è stata del 62% a 1 anno e del 46% a 2 anni. Nessun paziente ha avuto un miglioramento della funzionalità uditiva con la RFS. Il trattamento è stato generalmente ben tollerato. Due pazienti hanno necessitato di intervento chirurgico per degenerazione cistica del tumore. Due paziente hanno avuto uno spasmo del nervo facciale permanente che è regredito con la terapia medica. Un paziente ha sviluppato una neuropatia del trigemino dopo circa 2 anni dal trattamento. Conclusioni: La RFS rappresenta una valida alternativa terapeutica relativamente non-tossica per i NA anche nei casi di tumori di grandi dimensioni. Il controllo tumorale è sovrapponibile a quello che si ottiene con la radiosurgery o con il trattamento radioterapico convenzionale. Un più lungo follow-up è necessario per valutare il controllo tumorale a lungo termine.Purpose: Analysis of tumour control and cranial nerve function preservation for patients treated with Fractionated Stereotactic Radiotherapy (FSRT) for acoustic neuromas (AN). Patients and Methods: From May 1999 and to September 2003, 29 patients with AN have been treated by FSRT. Twenty-eight patients received a dose of 50Gy and 1 received 20Gy because of poor performance status. The median follow up was 23 months. We evaluated tumour control rate, cranial nerve preservation and other treatment-related toxicity. Results: The tumour control rates was 100% at 3years. None of these patients required surgical operation for tumour progression. Two patients needed surgery for cystic degeneration of the tumour. Two patients complained chronic haemi-facial spasms, which were well controlled with medical therapy and a patient developed ipsilateral moderate facial dysfunction. Two patients developed trigeminal neuropathy approximately 2 year and 5 months after treatment. The hearing preservation was 68% at 1 year and 51% at 2 year. None of our patients showed improvement on hearing level. Conclusion: FSRT is valid and safe treatment for AN, either as primary treatment or as treatment for progressive residual disease. SFRT consents alto to treat large tumor volume with low risk on developing major neurological complication. Longer follow up will be required to assess the durability of tumour contro

Obesity and Breast Cancer: Interaction or Interference with the Response to Therapy?

Background: Aromatase inhibitors (AI) are widely used for treating hormone-sensitive breast cancer (BC). Obesity, however, due to aromatase-mediated androgen conversion into estradiol in the peripheral adipose tissue, might impair AI inhibitory capacity. We aimed at identifying a cut-off of body mass index (BMI) with significant prognostic impact, in a cohort of stage I-II BC patients on systemic adjuvant therapy with AI. Methods: we retrospectively evaluated routinely collected baseline parameters. The optimal BMI cut-off affecting disease-free survival (DFS) in AI-treated BC patients was identified through maximally selected rank statistics; non-linear association between BMI and DFS in the AI cohort was assessed by hazard-ratio-smoothed curve analysis using BMI as continuous variable. The impact of the BMI cut-off on survival outcomes was estimated through Kaplan–Meier plots, with log-rank test and hazard ratio estimation comparing patient subgroups. Results: A total of 319 BC patients under adjuvant endocrine therapy and/or adjuvant chemotherapy were included. Curve-fitting analysis showed that for a BMI cut-off >29 in AI-treated BC patients (n = 172), DFS was increasingly deteriorating and that the impact of BMI on 2-year DFS identified a cut-off specific only for the cohort of postmenopausal BC patients under adjuvant therapy with AI. Conclusion: in radically resected hormone-sensitive BC patients undergoing neoadjuvant or adjuvant chemotherapy and treated with AI, obesity represents a risk factor for recurrence, with a significantly reduced 2-year DFS

The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies

Immune checkpoint inhibitors (ICIs) have a modest clinical activity when administered as monotherapy against breast cancer (BC), the most common malignancy in women. Novel combinatorial strategies are currently being investigated to overcome resistance to ICIs and promote antitumor immune responses in a greater proportion of BC patients. Recent studies have shown that the BC abnormal vasculature is associated with immune suppression in patients, and hampers both drug delivery and immune effector cell trafficking to tumor nests. Thus, strategies directed at normalizing (i.e., at remodeling and stabilizing) the immature, abnormal tumor vessels are receiving much attention. In particular, the combination of ICIs with tumor vessel normalizing agents is thought to hold great promise for the treatment of BC patients. Indeed, a compelling body of evidence indicates that the addition of low doses of antiangiogenic drugs to ICIs substantially improves antitumor immunity. In this review, we outline the impact that the reciprocal interactions occurring between tumor angiogenesis and immune cells have on the immune evasion and clinical progression of BC. In addition, we overview preclinical and clinical studies that are presently evaluating the therapeutic effectiveness of combining ICIs with antiangiogenic drugs in BC patients