Spine Instability Neoplastic Score (SINS) as a Predictive Tool in Conventional Radiotherapy: A Narrative Review.

AIMS: This narrative review seeks to identify the SINS score application in the radiation oncology field. METHODS: This literature review was performed searching papers on MEDLINE published from January 2010 to August 2022. RESULTS: In terms of vertebral painful lesions and RT symptomatic responses, the SINS score could be an interesting aid in order to choose the right therapeutic approach. Lesions with higher level of instability, and therefore higher SINS score, could did not find any significant benefit from radiation therapy which is more effective on the tumor-related pain component. For SINS as a predictor of adverse event after RT or its changes after RT, we obtained contrasting results. CONCLUSIONS: The reported few experiences showed ambiguous conclusions. Further prospective studies are needed.

Stereotactic radiotherapy in intrahepatic cholangiocarcinoma: A systematic review.

Among biliary tract cancers, intrahepatic cholangiocarcinoma (ICC) has different characteristics compared with those in other sites. Current guidelines suggest several treatment options for ICC, including stereotactic body radiation therapy (SBRT). However, the role of SBRT in locally advanced ICC is unclear. The aim of the present study was to present a systematic review on the efficacy and safety of SBRT in ICC. A systematic review based on the PRISMA methodology was performed. Only papers reporting outcomes in terms of overall survival (OS) after SBRT in inoperable patients with ICC were included. Secondary aims were local control (LC), progression-free survival (PFS) and treatment-related toxicity. Six papers (145 patients) were included in the present analysis. SBRT was frequently used as a salvage treatment, since 28.6-66.7% of patients received previous systemic or local treatments. The median SBRT dose was 45 Gy delivered in 3-5 fractions. The median follow-up was 16 months, and median OS time was 14 months (range, 10-48 months). In one of the included studies, SBRT was significantly superior in terms of OS compared with both chemoradiation and trans-arterial-radio-embolization. The 1-year LC rate was 85% in one study, and 1-year PFS rates were 50 and 68% in two studies, respectively. Toxicity was generally not reported in detail or was reported including other sites of biliary cancers. Overall, limited evidence was available on the efficacy of SBRT in ICC, which should be further investigated in prospective studies with a larger number of patients. However, based on the available data, SBRT seems to produce similar results compared with other ICC treatments, with the advantage of being a very short and non-invasive therapy. Therefore, SBRT should be considered in selected patients with ICC.

Radiotherapy as treatment option in biliary cancer patients: a national survey of AIRO (Italian Association of Radiation Oncology) Gastroenterology Group.

BACKGROUND: The aim is to find out how many radiation oncology centres treat biliary duct carcinoma (BDC), what treatments they offer and whether they would be interested in developing prospective trials. MATERIALS AND METHODS: A questionnaire was posted to all 220 Italian Radiation Oncology Centres. The survey consisted of 31 eligibility questions in a combination of multiple and forced choice formats addressing the following parameters: characteristics of the centre, numbers of BDC patients treated, treatment options, radiotherapy parameters (target definition, schedule, technique, dose constraints) and interest in developing future randomized trials. RESULTS: No major differences emerged in BDC management, whatever the site, and whether it was resectable or not. Discrepancies in routine clinical practice were, however, observed with lack of agreement on expansion margins, dose constraints and treatment schedules for the stereotactic technique and palliative treatments. CONCLUSIONS: The present survey attempted to fill the gaps in the role of radiotherapy in patients with BDC. Since lack of prospective randomized studies and disease rarity have mitigated against an evidence-based approach, patients with BDC should be enrolled in prospective studies. The above-mentioned results should also emphasize the need to combine analysis of treatment results from all Italian centres in order to create predictive models.

Interventional radiotherapy as exclusive treatment for primary nasal vestibule cancer: single-institution experience.

PURPOSE: The aim of this paper was to evaluate treatment outcomes following interventional radiotherapy (brachytherapy - BT) for nasal vestibule cancer. MATERIAL AND METHODS: Considering histological diagnosis and staging, a multidisciplinary tumor board indicated an exclusive interventional radiotherapy for all patients. Plastic tubes were placed mainly with interstitial approach. The total dose was 44 Gy in 14 fractions, 3 Gy/fraction (except for the first and last fractions, 4 Gy), 2 fractions per day (b.i.d.), 5 days a week. Inclusion criteria for this analysis were: patients affected by squamous cell carcinoma with follow-up more than 6 months. RESULTS: 20 patients with primary nasal vestibule cancer were treated with IRT from May 2012 to June 2019. We excluded 4 patients due to follow-up less than 6 months and 2 patients affected by basal cell carcinoma. In total, 14 consecutive previously untreated patients were considered for definitive analysis, median age was 67.5 (range, 51-83) years, median follow-up was 53 (range, 6-84) months. All patients followed the protocol except one, who received a total dose of 42 Gy in 12 fractions, 3 Gy per 6 fractions, and 4 Gy per 6 fractions. Local control at 12, 24, and 36 months was 85.7%. Overall survival at 12 months was 92.3%, at 24 months was 76.9%, and at 36 months was 69.2%. Staging system proposed by Wang was statistically significant on local control (LC), disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). Excellent cosmetic results were observed. CONCLUSIONS: This study confirms that interventional radiotherapy could be considered as a definitive treatment in nasal vestibule cancer with excellent oncological and cosmetic outcomes.

Intraluminal Brachytherapy in Unresectable Extrahepatic Biliary Duct Cancer: An Italian Pooled Analysis.

BACKGROUND/AIM: To evaluate the outcome of patients with unresectable extrahepatic cholangiocarcinoma (CC) treated with external-beam radiotherapy (EBRT) and concurrent chemotherapy (CT) with or without intraluminal brachytherapy (ILBT) boost or with definitive ILBT. PATIENTS AND METHODS: A pooled analysis of patients with non-metastatic unresectable CC was performed. They were treated in three different institution with EBRT plus CT with or without an ILBT boost. Some patients received only ILBT with curative dose. RESULTS: Seventy-three patients were included in the analysis. Thirty-nine patients (53%) received EBRT treatment with ILBT boost (18 patients with CT during EBRT), while 28 patients (38%) were treated with EBRT (CT in 26 patients) and 6 patients (8.2%) with definitive ILBT (2 patients with CT). CT was administered including either the use of gemcitabine or 5-fluorouracil. With a median follow-up of 16 month (range=1-94 months), median overall survival (OS) was 16 months. Overall median LC was 16 months and patients who underwent ILBT had a better local control (LC) (p=0.018). CONCLUSION: The role of ILBT in unresectable CC is not yet supported by robust evidence in the literature. However, within this limit, preliminary results seem to suggest an improved local control in patients treated with ILBT, almost comparable to the ones of standard chemo-radiotherapy (CRT).

Optimized stereotactic volumetric modulated arc therapy as an alternative to brachytherapy for vaginal cuff boost. A dosimetric study.

We evaluate the role of stereotactic body radiotherapy using volumetric modulated arc therapy (VMAT) technique as an alternative to high-dose rate brachytherapy (HDR-BT) in the treatment of vaginal cuff in postoperative endometrial cancer. CT scans of 8 patients were used in this study. The clinical target volume (CTV) was defined as the 0.5 cm tissue around the applicator (then subtracting the applicator). Total dose was 30Gy delivered in 5 fractions. In HDR-BT, dose was prescribed at a distance of 0.5 cm from the surface applicator. For VMAT irradiation, a planning target volume (PTV) was obtained from CTV by an expansion of 3 mm. Two VMAT plans were generated using a full arc rotation. The first plan was optimized with an anatomy-based optimization module (PO-VMAT) using a 1mm multileaf collimator beam margin to enhance dose heterogeneity and dose fallout outside the target. The second plan was generated with a full-inverse planning module (FI-VMAT). Conformity (CI100, CI50, CI25), gradient (GI) indexes, and integral doses were calculated. To account for various dose heterogeneity distributions we calculated the equivalent uniform dose (EUD) using the Niemerko model. A Kruskal-Wallis analysis of variance followed by Dunn's-type multiple comparisons was performed. Dose distributions were more heterogeneous with HDR-BT: Dmean was 144.2% of prescription dose for CTV in HDR-BT and 118.5 and 108.6% for PTV in PO-VMAT and FI-VMAT, respectively. The mean values of EUD for CTV were 136.9%, 130.0 %, and 111.0% of prescription dose in HDR-BT, PO-VMAT, and FI-VMAT plans, respectively. GI indexes were 2.81, 3.41, and 4.14 for HDR-BT, PO-VMAT, and FI-VMAT, respectively. Near-maximal doses (D0.1cc) for rectum and bladder were significantly higher in HDR-BT plans compared to PO-VMAT and FI-VMAT plans (rectum: 131.2% vs112.8% vs 112.0%, respectively; bladder: 129.2% vs 108.7%, and 109.8%, respectively). PO-VMAT plans were able to mimic the HDR-BT dose distribution, showing a successful capability of highly conformal dose distribution, EUD values similar to HDR-BT, and steep dose-gradient outside PTV, then providing a reasonable alternative to brachytherapy.

HDR interventional radiotherapy (brachytherapy) in the treatment of primary and recurrent head and neck malignancies.

BACKGROUND: Interventional radiotherapy (brachytherapy; IRT) reemerged in the last decades as a potentially useful tool in head and neck oncology after a set of clear technical improvements were developed. METHODS: Sixty-one high dose ratio (HDR) IRT treatments were recommended and performed on 58 patients. We classified the cases into four relatively homogeneous groups based on the clinical needs that led to the recommended IRT. Also, we separately evaluated primary and recurrent cases. RESULTS: Disease-specific survival was significantly different among the four treatment groups. The group with the best prognosis was the cohort treated locally by exclusive interstitial IRT for resectable midface malignancies (2-year relapse-free survival = 82%, disease-specific survival = 89%). CONCLUSION: HDR IRT is a valuable tool in well-defined clinical situations and, in particular, in recurrences. In midface malignancies, it could become the preferred primary treatment.

An atlas for clinical target volume definition, including elective nodal irradiation in definitive radiotherapy of biliary cancer.

Radiotherapy (RT) is a treatment option for advanced biliary tract cancer (BTC), often combined with sequential and/or concurrent chemotherapy. The use of modern RT techniques requires accurate clinical target volume (CTV) definition and delineation. However, guidelines for CTV delineation in BTC are lacking. Therefore, the aim of this study was to propose a computer tomography (CT) atlas for CTV definition of BTC. We previously proposed guidelines to define the nodal CTV (CTV-N) in BTC. In this study, based on a literature analysis, we defined the margins to be added to the gross tumor volume (GTV; subclinical and microscopic disease) to define the primary tumor CTV (CTV-T). An abdominal contrast enhanced planning CT scan was performed on three different patients with unresectable intrahepatic cholangiocarcinoma (CC), extrahepatic CC and gallbladder cancer. The GTV and anatomical reference structures were outlined on CT images. Then, based on our guidelines, the CTV-T and CTV-N were delineated and merged to define the final CTV in the three patients. An atlas, showing the defined CTV, was generated from the reference CT images to illustrate the CTV for intra-hepatic CC, extra-hepatic CC and gallbladder cancer. This atlas can be used as an aid for CTV definition in patients with BTC treated with modern RT techniques.

Comparison of interstitial brachytherapy and surgery as primary treatments for nasal vestibule carcinomas.

OBJECTIVES/HYPOTHESIS: Squamous cell carcinoma arising from the nasal vestibule is a rare condition accounting for about 1% of head and neck malignancies with several peculiarities concerning both staging and treatment. The aim of this study was to compare the oncological and functional results of two different treatment modalities for the primary site: surgery and brachytherapy. STUDY DESIGN: A case series with the comparison of two different treatment modalities. METHODS: We evaluate clinical and survival data of 12 untreated patients, enrolled by a multidisciplinary tumor board, comparing oncological, functional, and esthetic results after surgery or after interstitial brachytherapy as exclusive treatments for the primary site. The functional and esthetic outcome was subjectively rated by the patients using a five-point scale. RESULTS: Locoregional control and survival are not significantly different between patients primarily treated by surgery and by brachytherapy. The functional and esthetic outcome, as assessed by the degree of satisfaction of the patients, is significantly better after primary brachytherapy than after primary surgery (P = .014). CONCLUSIONS: In our experience brachytherapy, accomplished in close cooperation between surgeons and radiation oncologists, achieves oncological results that are not different from surgery, but with a higher degree of patient satisfaction, mainly due to the esthetic outcome. LEVEL OF EVIDENCE: 4.

Radiosurgery or Fractionated Stereotactic Radiotherapy plus Whole-brain Radioherapy in Brain Oligometastases: A Long-term Analysis.

AIM: To analyze the outcome of patients with brain oligometastases treated by radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) after whole-brain radiotherapy (WBRT). PATIENTS AND METHODS: Overall survival (OS) and local control (LC) were evaluated in patients (patients) with 1-2 brain metastases. RESULTS: Forty-seven patients were selected. They were submitted to WBRT (median dose=3,750 cGy) followed by SRS (17 patients; median dose=1,500 cGy) or FSRT (30 patients; median dose=2,000 cGy). Median follow-up was 102 months (range=17-151); the median survival was 22 months for the SRS group and 16 months for the FSRT group. One-year and 5-year survival was 56% and 16%, respectively, in SRT and 62.1% and 3%, respectively, in FSRT. Neither treatment proved to significantly impact OS (p=0.4). The 1-year LC rates were 80% and 61.1% in the two groups, respectively (p=0.15). CONCLUSION: SRS or FSRT after WBRT could offer the same outcomes in patients with brain oligometasteses. Further investigation is warranted to confirm these data and define the optimal stereotactic modality.

Adjuvant Chemoradiation in Pancreatic Cancer: A Pooled Analysis in Elderly (≥75 years) Patients.

AIM: To determine the impact of postoperative chemoradiation (POCR) on overall survival (OS) after resection of pancreatic adenocarcinoma (PAC) in elderly (≥75 years) patients. MATERIALS AND METHODS: A multi-center retrospective review of 1248 patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive PAC was performed. Exclusion criteria included age <75 years, metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiotherapy (IORT) and postoperative death. RESULTS: A total of 98 patients were included in the analysis (males=39.8%, females=60.2%; R1 resections=33.7%; pN1=61.2%); 63 patients received POCR and 26 patients received adjuvant chemotherapy alone. The median follow-up was 25.6 months. The mean age for the entire cohort of patients was 78.1±2.9 (SD) years. No differences were observed between patients receiving or not receiving POCR in terms of age (p=0.081), tumor diameter (p=0.412), rate of R1 resection (p=0.331) and incidence of lymph node-positive disease (p=0.078). The only factor predicting an improved OS was POCR. The median OS was 69.0 months in patients treated by POCR and 23.0 months in patients treated without POCR (p=0.008). Even by Cox multivariate analysis, the only significant predictor of OS was POCR (hazard ratio=0.449; 95% confidence interval=0.212-0.950; p=0.036). CONCLUSION: The study represents the first comparative approach on POCR in elderly patients after resection of PAC. OS was higher in patients who received POCR. Further analyses are warranted to evaluate the toxicity rate/grade and the impact of POCR on patient quality of life.

Multi-institutional pooled analysis on adjuvant chemoradiation in pancreatic cancer.

PURPOSE: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. METHODS AND MATERIALS: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462 patients received adjuvant CT. RESULTS: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014) CONCLUSION: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT.

A feasibility study of neo-adjuvant low-dose fractionated radiotherapy with two different concurrent anthracycline-docetaxel schedules in stage IIA/B-IIIA breast cancer.

AIMS AND BACKGROUND: The aim of the study was to evaluate the feasibility of neoadjuvant low-dose fractionated radiotherapy, in combination with two anthracycline-docetaxel regimens, in breast cancer treatment. MATERIALS AND METHODS: Women with stage IIA/B-IIIA breast cancer were assigned to receive the treatment of low-dose fractionated radiotherapy (0.4 Gy/per fraction, 2 fractions per day, for 2 days, every 21 days for 8-6 cycles) with concomitant neoadjuvant chemotherapy with non-pegylated liposomal doxorubicin and docetaxel. Two chemotherapy schedules were planned to be combined with low-dose fractionated radiotherapy. The first schedule consisted of four cycles of non-pegylated liposomal doxorubicin sequentially followed by four cycles of docetaxel, and the second schedule consisted of six cycles of non-pegylated liposomal doxorubicin plus concomitant docetaxel. Acute toxicity was evaluated according to the Radiation Therapy Oncology Group score system. Pathological response was evaluated by the Mandard score and expressed as tumor regression grade. RESULTS: Between March 2008 and February 2009, 10 patients underwent low-dose fractionated radiotherapy and concomitant chemotherapy. No grade 3-4 breast toxicity was observed. Five patients had a clinical complete response. Seven patients underwent conservative surgery. Overall, tumor regression grade 1 (absence of residual cancer) was achieved in one patient (10%) and grade 2 (residual isolated cells scattered through the fibrosis) in 4 patients (40%). The pathologic major response rate (tumor regression grade 1 + 2) was 20% in patients receiving low-dose fractionated radiotherapy and sequential non-pegylated liposomal doxorubicin and docetaxel and 80% in the group receiving low-dose fractionated radiotherapy and concurrent non-pegylated liposomal doxorubicin and docetaxel treatment. CONCLUSIONS: Concomitant low-dose fractionated radiotherapy combined with anthracycline and docetaxel is feasible. The toxicity profile of radio-chemotherapy was similar to that of chemotherapy alone: there was no acute skin or cardiac toxicity. The concurrent application of liposomal doxorubicin and docetaxel with low-dose fractionated radiation led to higher histological response rates compared to the sequential application of the same two drugs.

Locally advanced prostate cancer: three-dimensional magnetic resonance spectroscopy to monitor prostate response to therapy.

PURPOSE: To correlate results of three-dimensional magnetic resonance spectroscopic imaging (MRSI) with prostate-specific antigen (PSA) levels and time since external beam irradiation (EBRT) in patients treated with long-term hormone therapy (HT) and EBRT for locally advanced disease to verify successful treatment by documenting the achievement of metabolic atrophy (MA). METHODS AND MATERIALS: Between 2006 and 2008, 109 patients were consecutively enrolled. MA was assessed by choline and citrate peak area-to-noise-ratio <5:1. Cancerous metabolism (CM) was defined by choline-to-creatine ratio >1.5:1 or choline signal-to-noise-ratio >5:1. To test the strength of association between MRSI results and the time elapsed since EBRT (TEFRT), PSA levels, Gleason score (GS), and stage, logistic regression (LR) was performed. p value <0.05 was statistically significant. The patients' outcomes were verified in 2011. RESULTS: MRSI documented MA in 84 of 109 and CM in 25 of 109 cases. LR showed that age, GS, stage, and initial and recent PSA had no significant impact on MRSI results which were significantly related to PSA values at the time of MRSI and to TEFRT. Patients were divided into three groups according to TEFRT: <1 year, 1-2 years, and >2 years. MA was detected in 54.1% of patients of group 1, 88.9% of group 2, and in 94.5% of group 3 (100% when PSA nadir was reached). CM was detected in 50% of patients with reached PSA nadir in group 1. Local relapse was found in 3 patients previously showing CM at long TEFRT. CONCLUSION: MA detection, indicative of successful treatment because growth of normal or abnormal cells cannot occur without metabolism, increases with decreasing PSA levels and increasing time on HT after EBRT. This supports long-term HT in advanced prostate cancer. Larger study series are needed to assess whether MRSI could predict local relapse by detecting CM at long TEFRT.

Intra-operative radiotherapy (IORT) in pancreatic cancer: joint analysis of the ISIORT-Europe experience.

PURPOSE: A joint analysis of data from five contributing centers within the ISIORT-Europe program was performed to investigate the main contributions of intra-operative radiotherapy (IORT) to the multidisciplinary treatment of pancreatic cancer. MATERIALS AND METHODS: Patients with a histologic diagnosis of carcinoma of the pancreas, with an absence of distant metastases, undergoing surgery with radical intent and IORT were considered eligible for participation in this study. RESULTS: From 1985 to 2006, a total of 270 patients were enrolled in the study from five European institutions. Surgery was performed in 91.5% of cases and complicated by adverse events in 59 cases. External radiotherapy (ERT) preceded surgery in 23.9% of cases. One-hundred and six patients received further ERT. After surgery + IORT, median follow-up was 96 months (range 3-180). Median local control was 15 months, 5-year local control was 23.3%. Median overall survival was 19 months, while 5-year survival was 17.7%. A significantly greater local control and survival were observed in patients undergoing preoperative radiotherapy (LC: median not reached; OS: median 30 months) compared to patients treated with postoperative ERT alone (LC: median 28 months; OS: median 22 months), and to patients submitted to IORT exclusively (LC: median 8 months; OS: median 13 months) (p < 0.0001). CONCLUSION: From this joint analysis emerges the fact that preoperative radiotherapy increases the effects of IORT in terms of local control and overall survival. The 5-year local control of 23.3% confirms the beneficial "sterilizing" effect of IORT on the tumor bed.

Radiation therapy of breast cancer. Reasoned approach to a clinical case.

The case of a patient undergoing quadrantectomy of lower quandrants of the right breast and ipsilateral axillary lymph node dissection for breast cancer followed by adjuvant radiotherapy is discussed. The stage of the disease and prognostic factors are analyzed for prognosis. Comorbidities ruled out chemotherapy. Radiation therapy was planned followed by clinicoinstrumental controls. After the second control ipsilateral costal bone metastases were observed; radiation therapy for palliation was prescribed.