Papers by Vincenzo Tombolini
Journal of Personalized Medicine, 2021
In head and neck cancer management, there is a need for tailored approaches to optimally implemen... more In head and neck cancer management, there is a need for tailored approaches to optimally implement clinical outcomes. Based on the assumption that efficacy and long-term toxicity are not satisfactory for standard concurrent platinum-based chemoradiotherapy, several trials have been designed to test whether induction immunotherapy and/or concomitant immunotherapy and radiotherapy result in improved survival and toxicity outcomes. Here, we present an overview of the most recent concomitant therapeutic strategies for head and neck cancer, focusing on the knowledge available regarding check-point inhibitors. The aim is to present the characteristics of the main check-point inhibitors and to summarize the clinical trials on the combination of immune check-point inhibitors and (chemo)radiotherapy in the definitive HNC setting, in order to provide a useful clinical tool for further research.
Acta Haematologica, 2020
Introduction: Patients with cancer may be more susceptible to and have higher morbidity and morta... more Introduction: Patients with cancer may be more susceptible to and have higher morbidity and mortality rates from COVID-19 than the general population, while epidemiologic data specifically addressed to hematologic patients are limited. To investigate whether patients with hematologic diseases undergoing therapy are at increased risk for acquiring SARS CoV-2 infection compared to the general population, a retrospective study was carried out at a referral hematologic center in Rome, Italy, during the period of the greatest epidemic spread (March 8 to May 14, 2020). Methods: All adult and pediatric patients with a diagnosis of a neoplastic or a nonneoplastic hematologic disease who underwent treatment (chemotherapy or immunosuppressive or supportive therapy) during the study period or in the previous 6 months were considered. The prevalence of COVID-19 in the overall outpatient and inpatient population undergoing hematologic treatment compared to that of the general population was anal...
In Vivo, 2020
Background/Aim: Intensity modulated radiotherapy (IMRT) has been compared with three-dimensional ... more Background/Aim: Intensity modulated radiotherapy (IMRT) has been compared with three-dimensional conformal radiotherapy (3D-CRT) in randomized clinical trials for head and neck squamous cell carcinoma (HNSCC). The aim of this meta-analysis was to evaluate the efficacy and toxicity of IMRT and 3D-CRT and identify differences in grade ≥2 xerostomia incidence and clinical outcomes. Materials and Methods: The preferred reporting items for systematic reviews and metaanalyses (PRISMA) statement was applied. Random-effects models were used. Primary endpoint was xerostomia of grade 2 or worse. Secondary endpoints were overall survival (OS) and loco-regional control (LRC). Results: Three randomized clinical trials representing 213 patients were identified. Global, grade ≥2 acute xerostomia and late xerostomia at 1 and 2 years after treatment were reduced with the IMRT technique (RR=0.71,
Nanomaterials, 2019
Oral cavity carcinoma (OCC) remains an ongoing public health problem. Emerging nanotechnology pro... more Oral cavity carcinoma (OCC) remains an ongoing public health problem. Emerging nanotechnology provides alternative treatment approaches. This review covers the up-to-date literature in the human OCC treatment field. We explored the growing body of evidence to reveal novel and highly promising diagnostic and therapeutic applications of nanotechnology in this field. Various types of nanoparticles have been tested for applications in OCC. Imaging modalities in addition to nanocarriers are discussed. The encouraging contribution of lymphotropic nanoparticles contrast in the diagnosis of metastatic cervical lymph nodes needs to be confirmed. The development of the sentinel lymph node procedure and photodynamic therapy may lead to breakthrough therapies in order improve clinical outcomes and quality of life. In this perspective, cancer nanotechnology has the potential to revolutionize the treatment of OCC patients.
Clinical Neurology and Neurosurgery, 2019
OBJECTIVE To explore therapeutic results of different radiotherapy (RT) dose schedules combined t... more OBJECTIVE To explore therapeutic results of different radiotherapy (RT) dose schedules combined to Temozolomide (TMZ)-RT treatment in newly diagnosed glioblastoma (GB), according to the O (6)-methylguanine-DNA methyltransferase (MGMT) methylation status. PATIENTS AND METHODS Patients with newly diagnosed GB received either standard (60-59.4 Gy) or reduced (54-52 Gy) dose radiation therapy (RT) with concurrent and adjuvant TMZ between June 2010 and October 2016. We retrospectively evaluated the therapeutic effectiveness of the RT ranges schedules in terms of overall survival (OS) with univariate and multivariate analysis, after analyzing the MGMT methylation status. RESULTS One hundred and seventeen patients were selected for the present analysis out of 146 total treated patients accrued. Seventy-two out of the selected cases received the standard RT-TMZ course (SDRT-TMZ) whereas the remaining 45 underwent the reduced dose schedule (RDRT-TMZ). The analysis according to the MGMT promoter methylation status showed that, in methylated-MGMT GB patients, SDRT-TMZ and RDRT-TMZ groups did not show different median OS (p = ns) according to the two RT schedules, independently by the extent of surgical resection. Instead, a difference in survival outcomes was confirmed in unmethylated-MGMT GB patients with better survival for patients undergoing to SDRT, particularly in sub-total resection. CONCLUSION In our experience, a reduction of radiation dose schedule does not seem to jeopardize survival in methylated-MGMT patients independently by the extent of resection. A therapeutic approach to a standard reduction of RT dose for the methylated subset of patients may be feasible and could deserve prospective trials for validation.
Oncotarget, Jan 29, 2017
This study aims to evaluate the feasibility of a magnetic resonance (MR) automatic method for qua... more This study aims to evaluate the feasibility of a magnetic resonance (MR) automatic method for quantitative assessment of the percentage of fibrosis developed within locally advanced rectal cancers (LARC) after neoadjuvant radiochemotherapy (RCT). A total of 65 patients were enrolled in the study and MR studies were performed on 3.0 Tesla scanner; patients were followed-up for 30 months. The percentage of fibrosis was quantified on T2-weighted images, using automatic K-Means clustering algorithm. According to the percentage of fibrosis, an optimal cut-off point for separating patients into favorable and unfavorable pathologic response groups was identified by ROC analysis and tumor regression grade (MR-TRG) classes were determined and compared to histopathologic TRG. An optimal cut-off point of 81% of fibrosis was identified to differentiate between favorable and unfavorable pathologic response groups resulting in a sensitivity of 78.26% and a specificity of 97.62% for the identifica...
Ecancermedicalscience, 2018
Due to substantial improvement in the diagnosis and treatment of gynaecologic cancers, a better u... more Due to substantial improvement in the diagnosis and treatment of gynaecologic cancers, a better understanding of patient care needs to be revised. We reviewed the literature related to fertility preservation strategies in gynaecological cancer and discussed current general management approaches. New technical modalities and patients' own desire for motherhood should be integral and paramount in the clinical evaluation to significantly contribute to preserving fertility in those women diagnosed with gynaecologic cancers during the reproductive years.
BMC cancer, May 12, 2017
Neoadjuvant fluoropirimidine (5FU)-based chemoradiotherapy (CRT) has been considered the standard... more Neoadjuvant fluoropirimidine (5FU)-based chemoradiotherapy (CRT) has been considered the standard of care for locally advanced rectal cancer (LARC). Whether addition of oxaliplatin (OXP) will further improve clinical outcomes is still debated. We conducted a meta-analysis to evaluate the role of OXP in this patient population. Literature searches were carried out in PubMed, Medline and Scopus databases. End points were overall survival (OS), disease free survival (DFS), local failure (LF) and distant failure (DF). Odd ratio (OR) with 95% confidence interval (CI) was calculated using random effects model. Four randomized trials were included. Patients treated with OXP-5FU CRT had significantly decreased DF (OR = 0.76; 95% CI, 0.60 to 0.97; p = 0.03) compared to standard CRT. OS, DFS and LF were not significantly different between groups. OXP significantly decreased DF, but does not improve OS e DFS compared to 5FU CRT. Precise role of OXP in neoadjuvant setting of LARC remains to be ...
Cancer Letters, 2017
The role of histone deacetylase (HDAC) 4 and 6 in glioblastoma (GBM) radioresistance was investig... more The role of histone deacetylase (HDAC) 4 and 6 in glioblastoma (GBM) radioresistance was investigated. We found that tumor samples from 31 GBM patients, who underwent temozolomide and radiotherapy combined treatment, showed HDAC4 and HDAC6 expression in 93.5% and 96.7% of cases, respectively. Retrospective clinical data analysis demonstrated that high-intensity HDAC4 and/or HDAC6 immunostaining was predictive of poor clinical outcome. In vitro experiments revealed that short hairpin RNA-mediated silencing of HDAC4 or HDAC6 radiosensitized U87MG and U251MG GBM cell lines by promoting DNA double-strand break (DSBs) accumulation and by affecting DSBs repair molecular machinery. We found that HDAC6 knock-down predisposes to radiation therapy-induced U251MG apoptosis-and U87MG autophagy-mediated cell death. HDAC4 silencing promoted radiation therapy-induced senescence, independently by the cellular context. Finally, we showed that p53 WT expression contributed to the radiotherapy lethal effects and that HDAC4 or HDAC6 sustained GBM stem-like radioresistant phenotype. Altogether, these observations suggest that HDAC4 and HDAC6 are guardians of irradiation-induced DNA damages and stemness, thus promoting radioresistance, and may represent potential prognostic markers and therapeutic targets in GBM.
Hematological Oncology, 2017
Our aim is to assess the incidence of second cancer in long‐time surviving primary mediastinal B‐... more Our aim is to assess the incidence of second cancer in long‐time surviving primary mediastinal B‐cell lymphoma (PMBCL) patients treated with combined radiochemoimmunotherapy (standard methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin with rituximab and mediastinal radiation therapy at a dose of 30 to 36 Gy). For this purpose, 92 points were evaluated. After a median overall survival of 137 months (range 76‐212), we recorded second cancer in 3 of 80 long‐surviving patients (3.75%) with cumulative incidence of 3.47% at 15 years and 11% at 17 years, with a 17‐year second cancer‐free survival of 82%. We observed 2 papillary thyroid cancers with a standardized incidence ratio (SIR) of 7.97 and an absolute excess risk (AER) of 17. 84 and 1 acute myeloid leukemia (AML) with an SIR of 66.53 and an AER of 10.05. No breast cancer occurred. Although we should take into account the limits of the proposed statistical analysis, combined mod...
Anticancer research, Sep 1, 2016
The aim of this study was to evaluate treatment-related toxicity and clinical outcomes of total b... more The aim of this study was to evaluate treatment-related toxicity and clinical outcomes of total body irradiation (TBI) in patients with acute lymphoblastic leukemia (ALL). We performed a retrospective review of all patients with ALL who underwent TBI-based conditioning regimen at our Institution between 2000 and 2012. A total of 211 patients were included. The median follow-up was 40 months. The 5-year overall survival and disease-free survival were 64.7% and 62.8%, respectively. The 5-year overall survival rate for the 163 children was 67.6% (95% confidence interval=55-77%). Disease status at time of transplant did not improve disease-free survival. Gastrointestinal acute toxicity was the most common early side-effect (19.9%). Acute graft-versus-host disease was reported in 31 patients (14.7%). Main late toxicities were cataract induction (12.8%) and growth, gonadal and endocrine effects (36%). TBI-based conditioning regimen led to a high survival rate with remarkably low radiation...
Anticancer research, Dec 1, 2016
To estimate the clinical outcomes of induction chemotherapy (IC) followed by standard chemoradiot... more To estimate the clinical outcomes of induction chemotherapy (IC) followed by standard chemoradiotherapy (CRT) and CRT alone in patients with locally advanced human papilloma virus (HPV)-negative oropharyngeal squamous cell carcinoma. Consecutive patients with histologically-proven HPV-negative squamous cell carcinoma of the oropharynx were included and treated with IC-CRT or CRT alone. In order to compare treatment outcomes and toxicity between groups, patients were matched by primary tumor site and clinical disease stage. Overall survival (OS), disease-free survival (DFS) and metastasis-free survival (MFS) curves were calculated with the Kaplan-Meier method. Nine IC patients and 18 CRT patients were included. All patients completed the programmed treatment. The median follow-up was 38 months. There were no statistically significant differences in OS and DFS between groups. The 5-year MFS was 88.9% and 50.8% in the IC-CRT group, respectively. There was no meaningful difference in to...
Anticancer Research, 2016
Aim: To evaluate whether patients with external sphincter invasion have a better prognosis than p... more Aim: To evaluate whether patients with external sphincter invasion have a better prognosis than patients with invasion of other organs. Patients and Methods: Patients with cT4b adenocarcinoma of the rectum were treated with a tri-modality approach, including neo-adjuvant chemoradiotherapy (CRT), surgery and adjuvant chemotherapy. Patients with external sphincter invasion were classified as cT4b1, whereas patients with invasion of other organs as cT4b2. Survival curves were compared for cT4b sub-stage. Results: Between January 2008 and December 2014, a total of 21 consecutive patients with cT4b disease (14 with cT4b1 and seven with cT4b2) were treated with CRT, followed by surgery and adjuvant chemotherapy. In total, the overall survival rate at 5 years was 57.4%, whereas 5-year disease-free survival was 52%. The 5-year overall survival rates were 65.3% and 44.4% for patients with cT4b1 and cT4b2 disease, respectively. Conclusion: External sphincter invasion seems to be associated with a better prognosis when compared to primary lesion with extension to other organs. Tumor and lymph node staging are paramount to treatment choices in patients with locally advanced rectal cancer (LARC). In rectal cancer, the stage system is still based on depth of penetration through the rectal wall (T), the presence and the number of metastatic lymph nodes (N), and the presence of distant metastasis (M). Throughout the years, minor changes have been made in relation to the T classification. In the seventh edition of the American Joint Committee on Cancer (AJCC) staging, T4 was stratified into T4a (tumor penetrates to the surface of the visceral peritoneum) and T4b (tumor directly invades or is adherent to other organs or structures), due to a 10% improvement in 5-year overall survival (OS) in patients with T4a compared to T4b lesions (1). However, cT4b appears to be grossly classified considering that invasion of other organs is merged with involvement of structures by virtue of extension beyond the muscularis propria (2). Thus, the placement of all patients with cT4b disease in the same T sub-stage, independently of invasion of organs, such as prostate, uterus, bladder or bowel, and structures including external sphincter, describes a heterogeneous group of lesions. This does not provide complete clinical information, and this feature could have a different prognostic significance and influence treatment decisions. The aim of this work was to determine whether patients with external sphincter invasion (cT4b1) have a better OS then those with invasion of other organs (cT4b2). Patients and Methods Patients. This study was approved by the Institutional Review Board (Prot. 464/16) and all patients signed an informed consent. A retrospective analysis of patients treated at our institute between January 2008 and December 2014 for cT4b adenocarcinoma of the rectum was performed. The main inclusion criteria were age over 18 years, no previous medical history of radiotherapy to the pelvic region, no metastatic disease at diagnosis, and clinical evidence of stage cT4b adenocarcinoma of the rectum. Local staging of disease was made by endorectal ultrasound and abdominal-pelvic computerized tomography (CT) with/without pelvic magnetic resonance imaging (MRI). Data were collected on local tumor invasion of organs or structures at the pre-treatment examination. The seventh AJCC Staging System was used for the TNM classification (3). Extension to the external sphincter was recorded as cT4b1, whereas tumor directly invading organs, including prostate, seminal vesicles, cervix or vagina, was defined as cT4b2. Pre-treatment investigation also included a chest CT scan. For all cases, demographic data (such as sex, age, smoking, alcohol, performance status) and primary tumor parameters (including localization, tumor stage, treatment modality, toxicity) were collected.
Oncotarget, 2016
Aim: Three weeks paclitaxel and carboplatin has been considered the standard of care for primary ... more Aim: Three weeks paclitaxel and carboplatin has been considered the standard of care for primary treatment of ovarian cancer (OC). Whether weekly therapy will further improve the clinical outcomes or not is still unclear. We conducted a metaanalysis to compare the two regimens. Method: Articles were selected with a systematic approach, using PubMed databases. Trials concerning comparison between carboplatin plus weekly paclitaxel (dose-dense regimen) and carboplatin plus paclitaxel every 3 weeks were considered. Outcomes included overall survival (OS), progression free survival (PFS) and severe acute toxicity. Results: Dose-dense regimen was associated with significant improvement of PFS compared with standard schedule, with HR of 0.73 (95% CI 0.61-0.88, p = 0.001). There was no difference in OS between treatment regimens (HR 0.95, 95% CI 0.77-1.16, p=0.06), as well as in term of severe acute toxicity. Conclusion: Dose-dense regimen is superior to standard schedule in terms of PFS. Further studies are necessary to firmly confirm this evidence in advanced OC treatment.
Oncotarget, Jan 16, 2016
Predictive factors of pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCR... more Predictive factors of pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) are still not identified. The purpose of this study was to define them. Data from consecutive LARC patients treated between January 2008 and June 2014 at our Institution were included in the analysis. All patients were treated with a long course of nCRT. Demographics, initial diagnosis and tumor extension details, as well as treatment modalities characteristics were included in the univariate and logistic regression analysis. In total 99 patients received nCRT, of whom 23 patients (23.2%) achieved pCR. Patients with and without pCR were similar in term of age, sex, comobidities, BMI and tumor characteristics. Multivariate logistic regression indicated that pre-treatment tumor size ≤ 5 cm was a significant predictor for pCR (p = 0.035), whereas clinical N stage only showed a positive trend (p = 0.084). Tumor size at diagnosis could be used to pr...
Oncotarget, Jan 8, 2015
To analyze the efficacy and toxicity of bevacizumab on survival outcomes in recurrent ovarian can... more To analyze the efficacy and toxicity of bevacizumab on survival outcomes in recurrent ovarian cancer. Bevacizumab was associated with significant improvement of PFS and OS compared with standard treatment with HRs of 0.53 (95% CI 0.44 - 0.63; p < 0.00001) and 0.87 (95% CI, 0.77 to 0.99; p = 0.03), respectively. Bevacizumab increased the incidence of G3/G4 hypertension (RR 19.01, 95% CI 7.77 - 46.55; p < 0.00001), proteinuria (RR 17.31, 95% CI 5.42 - 55.25; p < 0.00001), arterial thromboembolic events (ATE) (RR 4.99, 95% CI 1.29 - 19.27; p = 0.02) and bleeding (RR 3.14, 95% CI 1.35 - 7.32; p = 0.008). Three randomized phase III trials representing 1502 patients were identified. Pooled hazard ratio (HR), odd ratio (OR), risk ratio (RR) with 95% confidence interval (CI) were calculated using fixed or random effects model. Adding bevacizumab to standard chemotherapy improved ORR, PFS and OS, and it had a higher, but manageable, incidence of toxicities graded 3 to 4.
International Journal of Colorectal Disease, 2015
Anticancer research
The aim of this study was to evaluate the role of radiation therapy alone, employing standard fra... more The aim of this study was to evaluate the role of radiation therapy alone, employing standard fractionation, in stage III-IV hypopharyngeal carcinoma. Fourteen (38.9%) stage III and 22 (61.1%) stage IV patients with hypopharyngeal carcinoma were submitted, with curative intent, to exclusive radiotherapy to the primary tumor and regional draining lymph nodes, level II, III, IV, V and VI. Total dose ranged from 68 to 72 Gy. The 5-year overall survival (OS) and disease-specific survival (DSS) rates were 15.6% and 28.1%, respectively. Five-year OS in stage III and IV patients was, respectively, 33% and 5% (p=0.028) and DSS was, respectively, 50% and 16% (p=0.029). Five-year OS and DSS rate in N0 versus N+ patients were respectively 37.5% and 75% versus 8.3% and 12.5% (p=0.07 and p=0.05). Overall survival at 5 years for III-IV hypopharyngeal tumor treated with radiotherapy alone is poor. It is possible that the addition of the best radiation fractionation to the best concurrent chemother...
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Papers by Vincenzo Tombolini