A. Galuppi

Radiation-induced GADD45 expression correlates with clinical response to radiotherapy of cervical carcinoma

BACKGROUND Recent work has identified a category of genes devoted to the control of genomic stability and prevention of cellular evolution. They encode components of cell cycle checkpoint, i.e., regulatory pathways committed to ordered cell cycle transition and fidelity of replicated DNA under adverse environmental conditions, such as those following exposure to genotoxic agents. Gadd45 belongs to the class II family of DNA damage-inducible (DDI) gene, and its role in DNA repair has been proved in many experimental models. The aim of our study was to correlate gadd45 radio-induction with the responsiveness to radiotherapy of cervical carcinomas, a type of cancer most commonly treated with radiotherapy alone. METHODS By means of a competitive polymerase chain reaction strategy, we compared in 14 patients the gene expression levels before and during external beam radiotherapy, when a dose ranging from 18 to 25 Gy was delivered to the target. RESULTS We found a correlation between the lack of gadd45 induction and a good clinical response to radiotherapy, in terms of both local control and disease-free survival. CONCLUSION Our results support the measure of the induction of gadd45, and possibly of other genes required for regulated G1-S checkpoint, as a method useful for prognostic evaluation of cervical carcinoma patients.

MACOP-B Regimen Followed by Involved-Field Radiation Therapy in Early-Stage Aggressive Non-Hodgkin's Lymphoma Patients: 14-Year Update Results

A single-center, retrospective study was conducted to evaluate therapeutic results of the MACOP-B third-generation chemotherapy regimen followed by involved-field radiation therapy in a stage I-II aggressive non-Hodgkins lymphoma (NHL) patients. From 1986 to 1995, 118 consecutive patients with the diagnosis of aggressive NHL, stage I-IE or II-IIE, with or without bulky disease were treated with MACOP-B regimen followed, when appropriate, by 30–36 Gy involved-field radiation therapy The complete response (CR) rate was 95% after the combined modality treatment (97% for stage I-IE and 93% for stage II-IIE). Patients with bulky disease had a CR rate of 92%. Treatment was well tolerated and no deaths occurred from acute toxicity. After a median follow-up of 68 months, 24 (21%) patients relapsed. The 14-year projected relapse-free and overall survival rates were 78% and d 69%, respectively. MACOP-B regimen with/without involved-field radiation therapy provides a safe and effective combined modality treatment for early-stage aggressive NHL, with the possibility to definitively cure two thirds of the patients

ABVD and radiation therapy as first-line treatment in advanced Hodgkin's disease.

The purpose of this study was to evaluate the efficacy of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and radiotherapy in advanced Hodgkins disease. In addition, to evaluate whether patients with slow responding tumors could profit from the early change of treatment regimen [MOPP (mechloretamine, vincristine, procarbazine, and prednisone)] followed by radiation therapy or autologous bone marrow transplantation (ABMT). Finally, to evaluate treatment options for patients with both early and late relapses. A total of 78 patients with previously untreated stages IIA bulky, IIB, III (A and B), and IV (A and B) Hodgkins disease were treated with the ABVD regimen followed by radiotherapy. Patients with stages IIIB and IV (A and B) were re-staged after 4 ABVD courses of the treatment: slow responders (response less than 70%) underwent second-line treatment (MOPP) and eventually ABMT. Relapsed patients with a long initial complete response (> or = 12 months) were treated with second-line conventional treatment and those patients with a short initial complete response (< 12 months) underwent ABMT. The complete response (CR) rate was 91% after ABVD and radiation therapy. An additional 5 stage IIIB and IV patients whose therapy was switched after 4 cycles because of a slow response obtained a CR (3 after 2 MOPP courses plus radiotherapy and 2 after 2 MOPP courses followed by ABMT). Including these additional CRs, the overall CR rate was 97%. No episodes of clinical cardiopulmonary toxicity were observed. With a median follow-up time of 42 months, the 4-year relapse-free survival was 87%. The 4-year overall survival was 96%. Ten cases relapsed: all but one obtained a second CR with different approaches depending on the timing of relapse. The ABVD regimen appears to be effective and well tolerated confirming the validity of this four-drug regimen in the treatment of advanced Hodgkins disease. In addition, therapeutic choices based on the timing of the relapse and the use of re-staging after 4 cycles in order to identify slow responders can play an important role in increasing the number of cured patients.

Electrochemotherapy can be used as palliative treatment in patients with repeated loco-regional recurrence of squamous vulvar cancer: a preliminary study

OBJECTIVE Electrochemotherapy (ECT) is an attractive treatment for solid cutaneous tumours with a good response rate (55-92%). No studies have evaluated ECT performed in vulvar cancer. The aim of our study was to evaluate the safety, local tumour efficacy and relief of symptoms of ECT treatment in patients affected by recurrence of squamocellular vulvar cancer (V-SCC) unsuitable for standard treatments. METHODS We enrolled nine patients with histological diagnosis of recurrence of V-SCC. Intravenous bleomycin was injected under general sedation after an accurate mapping of all lesions and ECT was performed. Patients were reviewed after one, three and six months. Response to therapy was evaluated using RECIST criteria and quality of life (QoL) was evaluated via questionnaires. RESULTS The median age was 84 years (range 80-90 years). The main location of recurrences was the vulva (87.5%). Multiple lesions were present in 25% of cases. No peri-operative complications were observed. Response to therapy was complete in 62.5% of patients, partial in 12.5%, no change was observed in 12.5% and progression of disease in 12.5% of patients respectively. Evaluation of symptoms showed a significant reduction of pain, bleeding, odour (p < 0.04) and urinary discomfort (p < 0.04). We observed two relapses at four and seven months after treatment. After nine months fifty percent of patients were alive. CONCLUSIONS Our preliminary study showed that ECT is a suitable procedure in elderly patients with loco-regional vulvar cancer relapses. ECT can be used as palliative therapy and the treatment relieves symptoms and improves QoL.

Palliative electro-chemotherapy in elderly patients with vulvar cancer: A phase II trial.

The primary endpoint of this trial was to assess clinical response (cCR) of squamocellular vulvar cancer (V‐SCC) in elderly patients treated with electro‐chemotherapy (ECT). Secondary endpoints were symptoms relief and local tumor control.

Underuse of brachytherapy for the treatment of dysphagia owing to esophageal cancer. An Italian survey

BACKGROUND International guidelines strongly recommend brachytherapy as valid alternative or in addition to stenting in patients with dysphagia owing to esophageal cancer. However, for not well understood reasons, brachytherapy is definitively underused for the palliative treatment of malignant dysphagia. Aim of the current survey was to investigate the use of brachytherapy for the treatment of malignant dysphagia in Italy. METHODS A structured questionnaire was submitted to the 1510 members of the Italian Association of Radiation Oncologists (AIRO). These members refer to 177 centres of radiotherapy across Italy and in 68 (38.4%) of them brachytherapy is routinely performed. RESULTS Of the 1510 invited members, 178 completed the survey (11.7%). The answers provided by the 178 participants allowed to get information on 40 out of 68 brachytherapy centres (58.8%). Seven out of 40 (17.5%) centres perform brachytherapy of the oesophagus, in 3 out of 40 (7.5%) centres brachytherapy represents the first line of treatment. The main reason why brachytherapy is not routinely performed is the lack of experience. CONCLUSION Despite the strong recommendations of the international guidelines and the wide diffusion of brachytherapy centres across Italy, only very few of them routinely considered brachytherapy for the treatment of dysphagia due to esophageal cancer.

Adjuvant radiotherapy with brachytherapy boost in soft tissue sarcomas

Purpose The standard primary treatment for soft tissue sarcoma (STS) is a wide surgical resection, preceded or followed by radiotherapy. Purpose of this retrospective study was to assess the efficacy of perioperative brachytherapy (BRT) plus postoperative external beam radiation therapy (EBRT) in patients with intermediate-high risk STS. Material and methods BRT delivered dose was 20 Gy. External beam radiation therapy was delivered with 3D-technique using multiple beams. The prescribed dose was 46 Gy to the PTV. Neoadjuvant and adjuvant chemotherapy (CHT) was used in patients with potentially chemosensitive histological subtypes. The primary aim of the study was to analyze overall survival (OS) and local control (LC) in a large patient population treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Secondary objective was to identify prognostic factors for patients outcome in terms of LC, disease-free survival (DFS), and OS. Results From 2000 to 2011, 107 patients presenting 2-3 grade (FNLCC) primary or recurrent STS were treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Five-year LC and OS were 80.9% and 87.4%, respectively. At univariate analysis, a higher LC was recorded in primary vs. recurrent tumors (p = 0.015), and in lower limb tumors vs. other sites (p = 0.027). An improved DFS was recorded in patients with lower limb tumors vs. other sites (p = 0.034). Conclusions The combination of BRT and EBRT was able to achieve satisfactory results even in a patients population with intermediate-high risk STS. Patients with recurrent or other than lower limb sited tumors show a worse LC.

Brachytherapy in non melanoma skin cancer of eyelid: a systematic review.

Purpose Non melanoma skin cancers (NMSC) of eyelid are uncommon. Many treatments approach are available with surgery being considered as the gold standard. Radiotherapy is an effective alternative in patients unfit for surgery. Brachytherapy (BT) might be a better therapeutic option due high radiation dose concentration to the tumor and rapid dose fall-off resulting in normal tissues sparing. The aim of this review is to evaluate local control, toxicity, and functional cosmetic outcome of BT in NMSC of eyelid. Material and methods A systematic search of the bibliographic databases PubMed, Scopus, and Cochrane Library from the earliest possible date through October 2015 was performed. Only studies published in English were included. Results Six articles fulfilled the selection criteria and were included in our review. Due to high risk of bias, all studies were classified to provide a low level of evidence (according to Scottish Intercollegiate Guidelines Network Classification). No randomized controlled trials or case control studies were founded. Brachytherapy was well tolerated with acceptable toxicity and high local control rates (median: 95.2%). Functional and cosmetic outcome were reported in five study as acceptable good functional-cosmetic outcome (median: 100%). Conclusions To date, few evidences are available on the role of BT in eyelid NMSC, and they show satisfactory results in terms of local control and functional cosmetic outcome. Therefore, prospective controlled trials are justified.

Electrochemotherapy pre-treatment in primary squamous vulvar cancer. Our preliminary experience

Previous studies showed a local tumor control of 80% in patients with relapsed squamous cell vulvar cancer (V‐SCC) treated with electrochemotherapy. These results encouraged electrochemotherapy use as neo‐adjuvant treatment in V‐SCC. The objective of this study was to evaluate the effectiveness of electrochemotherapy in reducing tumor burden in V‐SCC.

Brachytherapy boost after chemoradiation in anal cancer: a systematic review

Radio-chemotherapy (RCT) is the primary treatment of anal cancer (AC). However, the role and the optimal total dose of a radiation boost is still unclear. No randomized controlled trials nor systematic reviews have been performed to analyze the efficacy of brachytherapy (BRT) as boost in AC. Therefore, we performed this systematic review based on PRISMA methodology to establish the role of BRT boost in AC. A systematic search of the bibliographic databases: PubMed, Scopus, and Cochrane library from the earliest possible date through January 31, 2018 was performed. At least one of the following outcomes: local control (LC), loco-regional control (LRC), overall survival (OS), disease-free survival (DFS), or colostomy-free survival (CFS) had to be present for inclusion in this systematic review in patients receiving a BRT boost. Data about toxicity and sphincter function were also included. Ten articles fulfilled the inclusion criteria. All the studies had retrospective study design. All studies were classified to provide a level of evidence graded as 3 according to SIGN classification. Median 5-year LC/LRC, CFS, DFS, and OS were: 78.6% (range, 70.7-92.0%), 76.1% (range, 61.4-86.4%), 75.8% (range, 65.9-85.7%), and 69.4% (63.4-82.0%), respectively. The reported toxicities were acceptable. RCT is the treatment cornerstone in AC. High-level evidences from studies on BRT boost in AC are lacking. Further studies should investigate: efficacy of BRT boost in comparison to no boost and to external beam boost, patients who can benefit from this treatment intensification, and optimal radiation dose.