Maria Grazia Fabrini

Combined Nd-YAG laser/HDR brachytherapy versus Nd-YAG laser only in malignant central airway involvement: a prospective randomized study

BACKGROUND Laser debulking and prosthetic stents are useful modalities in the palliative treatment of initial inoperable or recurrent lung cancer. Recently, endobrochial brachytherapy was introduced to extend the duration of palliation and reduce the number of endoscopic treatments. This trial compares Nd-YAG laser alone and associated to high dose rated (HDR)-brachytherapy. PATIENTS AND METHODS From 1995 to 1998, 29 consecutive patients, with non-small cell lung cancer (NSCLC) and central airway involvement, were randomized in two groups: group 1 (15 patients) received Nd-YAG laser only; group 2 (14 patients) underwent a combined Nd-YAG laser/ HDR brachytherapy treatment. RESULTS There was no mortality or morbidity related to the treatment. The period free from symptoms was 2.8 months for group 1 and increased to 8.5 months in group 2 (P<0.05). The diseases progression free period grew from 2.2 months of group 1 to 7.5 months of group 2 (P<0.05) and the number of further endoscopic treatment reduced from 15 to 3 (P<0.05). CONCLUSION The results confirm the potential of brachytherapy to prolong relief from symptoms, lessen disease progression and reduce costs of treatment. A detailed analysis is presented of both groups.

Perioperative High-Dose-Rate Brachytherapy in the Treatment of Recurrent Malignant Gliomas

Purpose:To assess the feasibility and effectiveness of perioperative high-dose-rate brachytherapy for recurrent malignant gliomas.Patients and Methods:Between 2005 and 2008, 21 patients (14 males and seven females) with relapsed malignant glioma underwent a second surgery followed by a brachytherapy implant in the surgical cavity. Median age was 60 years, and median Karnofsky performance status 80. A single fraction of 18 Gy specified at 5 mm depth was administered perioperatively. Then, the applicator was removed nonsurgically. Mean postoperative hospitalization time was 3 days.Results:At the time of analysis, 15 patients (71%) had died and six (29%) were alive. Median follow-up was 32.3 months. Median overall survival from diagnosis amounted to 21.7 months. Median survival after recurrence was 8.0 months, and 6-month progression-free survival 42%. Patients were stratified into classes according to the prognostic recursive partitioning analysis.Conclusion:Perioperative brachytherapy has proven to be safe and well tolerated in patients with recurrent malignant glioma. No severe toxicity was reported, and the treatment has proven to be effective in symptomatic recurrences of malignant gliomas.Hintergrund und Ziel:Beurteilung der Durchführbarkeit und Wirksamkeit einer perioperativen High-Dose-Rate-(HDR-)Brachytherapie bei rezidivierenden malignen Gliomen.Patienten und Methodik:Zwischen 2005 und 2008 wurden 21 Patienten (14 Männer und sieben Frauen) mit rezidivierenden malignen Gliomen einer zweiten Operation zugeführt, gefolgt von einer HDR-Brachytherapie des Rezidivtumorbetts. Das durchschnittliche Alter der Patienten betrug 60 Jahre, der durchschnittliche Karnofsky-Performance-Status 80. Perioperativ wurde eine Einzeldosis von 18 Gy appliziert, dosiert auf 5 mm Gewebetiefe. Anschließend wurde der Applikator entfernt. Die mittlere Dauer des postoperativen Krankenhausaufenthalts lag bei 3 Tagen.Ergebnisse:Zum Zeitpunkt der Analyse waren 15 Patienten (71%) gestorben. Die mediane Nachbeobachtungszeit betrug 32,3 Monate. Die mediane Gesamtüberlebenszeit lag bei 21,7 Monaten. Das mediane Überleben nach Rezidivdiagnose betrug 8,0 Monate, das progressionsfreie 6-Monats-Überleben 42%. Die Patienten wurden gemäß der prognostischen RPA („recursive partitioning analysis“) in Klassen eingeteilt.Schlussfolgerung:Diese Untersuchung hat gezeigt, dass die perioperative HDR-Brachytherapie bei Patienten mit rezidivierten malignen Gliomen sicher und gut verträglich ist. Es wurde keine schwere Toxizität beobachtet. Die Ergebnisse bestätigen die Gültigkeit und Wirksamkeit einer solchen Behandlung bei symptomatischem Auftreten eines malignen Glioms.

Non-melanoma skin cancer treated with high-dose-rate brachytherapy and Valencia applicator in elderly patients: a retrospective case series

Purpose The incidence of non-melanoma skin cancer (NMSC) has been increasing over the past 30 years. Basal cell carcinoma and squamous cell carcinoma are the two most common subtypes of NMSC. The aim of this study was to estimate tumour control, toxicity, and aesthetic events in elderly patients treated with high-dose-rate (HDR) brachytherapy (BT) using Valencia applicator. Material and methods From January 2012 to May 2015, 57 lesions in 39 elderly eligible patients were enrolled. All the lesions had a diameter ≤ 25 mm (median: 12.5 mm) and a depth ≤ 4 mm. The appropriate Valencia applicator, 2 or 3 cm in diameter was used. The prescribed dose was 40 Gy in 8 fractions (5 Gy/fraction) in 48 lesions (group A), and 50 Gy in 10 fractions (5 Gy/fraction) in 9 lesions (group B), delivered 2/3 times a week. The biological effective dose (BED) was 60 Gy and 75 Gy, respectively. Results After median follow-up of 12 months, 96.25% lesions showed a complete response and only two cases presented partial remission. Radiation Therapy Oncology Group – European Organization for Research and Treatment of Cancer (RTOG/EORTC) G 1-2 acute toxicities were observed in 63.2% of the lesions: 56.3% in group A and 77.7% in group B. Late G1-G2 toxicities was observed in 19.3% of the lesions: 18.8% in group A and 22.2% in group B, respectively. No G3 or higher acute or late toxicities occurred. In 86% of the lesions, an excellent cosmetic result was observed (87.5% in group A and 77.8% in group B). Six lesions had a good cosmetic outcome and only 2.3% presented a fair cosmetic impact. Conclusions The treatment of NMSC with HDR-BT using Valencia surface applicator is effective with excellent and good cosmetics results in elderly patients. The hypofractionated course appears effective and no statistical differences were observed between the two groups analysed.

High-dose-rate brachytherapy in a large squamous cell carcinoma of the hand.

PURPOSE High-dose-rate (192)Ir-based brachytherapy can be used as an exclusive treatment of large skin tumors when teletherapy or surgery is not feasible. A case of an extended inoperable skin epithelioma of the hand is reported; the lesion involved the first finger, the tenar, the palm, and the back. METHODS AND MATERIALS A detailed description of an individual case is reported. A customized mold was created for the patient, to administer a fractionated brachytherapy treatment in a reproducible way. RESULTS A total dose of 50Gy was administered in 10 fractions, after a time schedule of three fractions per week. The treatment was well tolerated and the acute effects (mainly, epitheliolysis) were resolved completely within a month after the treatment. CONCLUSIONS Nine months after the treatment, the malignant lesion completely disappeared and the cosmetic results are quite satisfactory. Therefore, we conclude that the treatment technique is well adaptable to any particular geometry and that the fractionation scheme has proven to be well tolerated and effective in tumor eradication.

Squamous cell carcinoma of the vagina: natural history, treatment modalities and prognostic factors

Squamous cell carcinoma of the vagina accounts for less than 2% of all gynecologic malignancies. Surgery has a role in selected cases only. The standard treatment is radiotherapy, external beam radiation and/or brachytherapy, depending on the extent, thickness, location and morphology of the lesion. The role of chemotherapy is still under evaluation. Radiotherapy obtained 5-year overall survival rates ranged from 35% to 78%, with severe late complication rates of 9.4-23.1%. Tumor stage is the strongest prognostic factor. Tumor size >4cm, tumor location outside the upper third of the vagina, and old age at presentation are additional predictors of poor survival in most papers, whereas the prognostic value of histological grade, prior hysterectomy, and hemoglobin levels is controversial. High-risk HPV DNA and low MIB-1 index are associated with better clinical outcome. Because of the rarity of this tumor, future multicenter studies would be strongly warranted.

Non-melanoma skin cancer treated with high-dose-rate brachytherapy: a review of literature

Purpose The incidence of non-melanoma skin cancer (NMSC) has been increasing over the past 30 years. There are different treatment options and surgical excision is the most frequent treatment due to its low rates of recurrence. Radiotherapy is an effective alternative of surgery, and brachytherapy (BT) might be a better therapeutic option due to high radiation dose concentration to the tumor with rapid dose fall-off resulting in normal tissues sparing. The aim of this review was to evaluate the local control, toxicity, and cosmetic outcomes in NMSC treated with high-dose-rate BT (HDR-BT). Material and methods In May 2016, a systematic search of bibliographic database of PubMed, Web of Science, Scopus, and Cochrane Library with a combination of key words of “skin cancer”, “high dose rate brachytherapy”, “squamous cell carcinoma”, “basal cell carcinoma”, and “non melanoma skin cancer“ was performed. In this systematic review, we included randomized trials, non-randomized trials, prospective and retrospective studies in patients affected by NMSC treated with HDR-BT. Results Our searches generated a total of 85 results, and through a process of screening, 10 publications were selected for the review. Brachytherapy was well tolerated with acceptable toxicity and high local control rates (median: 97%). Cosmetic outcome was reported in seven study and consisted in an excellent and good cosmetic results in 94.8% of cases. Conclusions Based on the review data, we can conclude that the treatment of NMSC with HDR-BT is effective with excellent and good cosmetics results, even in elderly patients. The hypofractionated course appears effective with very good local disease control. More data with large-scale randomized controlled trials are needed to assess the efficacy and safety of brachytherapy.

A retrospective pooled analysis of response patterns and risk factors in recurrent malignant glioma patients receiving a nitrosourea-based chemotherapy

BackgroundAt recurrence the use of nitrosoureas is widely-used as a therapeutic option for glioblastoma (GBM) patients. The efficacy of fotemustine (FTM) has been demonstrated in phase II clinical trials; however, these papers report a wide range of progression-free-survival (PFS-6 m) rates, ranging from 21% to 52%. We investigated whether FTM could have a different response pattern in respect to time to adjuvant temozolomide failure, or whether specific independent risk factors could be responsible for the wide range of response rates observed.MethodsRecurrent GBM patients have been treated with fotemustine 75-100 mg/sqm at day 1, 8, 15 and after 4/5 weeks of rest with 100 mg/sqm every 21 days. Patients were stratified in 4 groups according to time to temozolomide failure: before starting (B0), during the first 6 months (B1), after more than 6 months of therapy (B2), and after a treatment-free interval (B3). Primary endpoint was PFS-6 m. A multivariable analysis was performed to identify whether gender, time after radiotherapy, second surgery and number of TMZ cycles could be independent predictors of the clinical benefit to FTM treatment.Results163 recurrent GBM patients were included in the analysis. PFS-6 m rates for the B0, B1, B2 and B3 groups were 25%, 28%, 31.1% and 43.8%, respectively. The probability of disease control was higher in patients with a longer time after radiotherapy (p = 0.0161) and in those who had undergone a second surgery (p = 0.0306).ConclusionsFTM is confirmed as a valuable therapeutic option for patients with recurrent GBM and was active in all study patient groups. Time after the completion of radiotherapy and second surgery are independent treatment-related risk factors that were predictive of clinical benefit.

A multimodal approach to the treatment of bilateral choroidal metastases from thyroid carcinoma

A 58-year old man, affected by metastatic thyroid carcinoma, experienced a progressive bilateral visual impairment. Ophthalmic examination revealed the presence of a choroidal mass with an associated exudative retinal detachment in both eyes. Twelve years before, a diagnosis of metastatic thyroid carcinoma had been established and the patient had been subject to several therapeutic procedures. In May 2007, he received a radiotherapy treatment to the left eye with an episcleral plaque and bilateral bulbar injection of bevacizumab. The patient had a rapid and stable visual acuity recovery. Twenty months after treatment, the lesion treated with radiotherapy was still stable whereas the contra-lateral lesion had evolved and determined a vitreal hemorrhage.

Stereotactic body radiotherapy of bone metastases in oligometastatic disease: prognostic factors of oncologic outcomes.

Background To evaluate the safety of stereotactic body radiotherapy (SBRT) of bone metastases in oligometastatic disease and to investigate prognostic factors of local control (LC), progression/disease-free survival (PDFS), and overall survival (OS). Methods Eligibility criteria were number of metastates ≤5, controlled primary tumor without evidence of progression under systemic therapy, exclusion of surgery, and no previous radiotherapy of the lesion of interest. Oligometastatic status was classified into only bone (BOD) and outside bone disease (OBOD), whereas SBRT was delivered to bone lesions using 2 different schedules: 24 Gy/1 fraction or 27 Gy/3 fractions. A positron emission tomography study of the lesion of interest was performed at baseline and at 3 months after SBRT to evaluate metabolic response according to European Organization for Research and Treatment of Cancer (EORTC) criteria. A Cox regression model was used for univariate and multivariate analysis. Results Between January 2010 and December 2013, 40 patients were enrolled. Only 1 patient experienced severe late toxicity (radiation-related fracture). Local control was longer among responders’ than nonresponders’ lesions (94.2% and 91.2% versus 63% and 35% at 1 and 2 years, respectively) (p = 0.004; hazard ratio = 9.958). The multivariate analysis of PDFS showed a significant correlation with planning target volume (PTV) size (p = 0.003) and oligometastatic status (p = 0.002). The multivariate analysis of OS confirmed a statistically significant value of the oligometastatic status (p = 0.002) and a significant trend for PTV size (p = 0.065). Conclusions Stereotactic body radiotherapy is safe with a low incidence of severe toxicity. Positron emission tomography response was a strong prognostic factor of LC whereas BOD status and small PTV size could identify a subset of oligometastatic patients at better prognosis.

Prognostic Significance of 2-Deoxy-2-[18F]-Fluoro-D-Glucose PET/CT in Patients With Locally Advanced Esophageal Cancer Undergoing Neoadjuvant Chemoradiotherapy Before Surgery: A Nonparametric Approach.

AbstractTo investigate the prognostic value of tumor metabolism measurements on serial 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography and computed tomography scans in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiotherapy.Forty-five patients (63 ± 7 years, 6 female) treated with concomitant chemoradiotherapy before surgery were followed up for 24 ± 18 months (range 4–71). Positron emission tomography and computed tomography scans were obtained within 1 week before the start (PET1) and 1 month after the completion of the treatment (PET2). Total body tumor metabolic activity was measured as the sum of the parameters: SUVmax, SUV corrected for lean body mass, and total lesion glycolysis (TLG40/50/70%). Then, delta values for the parameters between PET1 and PET2 were calculated and expressed as percentage of PET1 results.At the time of the analysis, 27 patients were dead and 18 were alive. There was no difference between the 2 groups in terms of age, sex, site of the disease, histology, and the presence/absence of linfonodal metastases (P = NS). Survival random forest analysis (20,000 trees) resulted in an estimate of error rate of 36%. The nonparametric approach identified &Dgr;TLG40 as the most predictive factor of survival (relative importance 100%). Moreover, T (17%), N (5%), and M (5%) stage of the disease, cancer histology (11%), TLG70 (5%) at the end of chemioradioterapy, and &Dgr;TLG50–70 (17%–5%) were positively associated with patient outcome.The nonparametric analysis confirmed the prognostic importance of some clinical parameters, such as TNM stage and cancer histology. Moreover, &Dgr;TLG resulted to be the most important factor in predicting outcome and should be considered in risk stratification of patients treated with neoadjuvant chemoradiotherapy.