Liver metastases and SBRT: A new paradigm?

BackgroundThe outstanding innovations made by early diagnosis, novel surgical techniques, effective chemotherapy regimens and conformal radiotherapy, have significantly improved patients overall survival and quality of life. Multidisciplinary approach to cancer has also led to an increased prevalence of patients with few, organ-confined metastases, who can experience long-term survival even if their disease is no longer localized. Liver is one of the most common site for metastatic disease from several cancers, and when metastatic disease is confined to liver, given the ability of this organ to regenerate almost to its optimal volume, surgical resection represents the standard of care because is associated with a better prognosis. Approximately 70–90% of liver metastases, however, are unresectable and a safe, effective alternative therapeutic option is necessary for these patients.Materials and methodsA review of the current literature was performed to analyze the role of SBRT in treating liver metastases from different cancers. A literature search using the terms “SBRT” and “liver metastases” was carried out in PUBMED.ResultsStereotactic body radiation therapy has shown to provide promising results in the treatment of liver metastases, thanks to the ability of this procedure to deliver a conformal high dose of radiation to the target lesion and a minimal dose to surrounding critical tissues.ConclusionStereotactic body radiation therapy is a non-invasive, well-tolerated and effective treatment for patients with liver metastases not suitable for surgical resection

Stereotactic radiotherapy for ultra-central lung oligometastases in non-small-cell lung cancer

Background: Stereotactic body radiotherapy (SBRT) in ultra-central (UC) lung tumors, defined in the presence of planning target volume (PTV) overlap or direct tumor abutment to the central bronchial tree or esophagus, may be correlated to a higher incidence of severe adverse events. Outcome and toxicity in oligometastatic (≤3 metastases) non-small-cell lung cancer (NSCLC) patients receiving SBRT for UC tumors were evaluated. Methods: Oligometastatic NSCLC patients treated with SBRT for UC were retrospectively reviewed. Local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) were calculated. Incidence and grade of toxicity were evaluated. Statistical analysis was performed to assess the impact of clinical and treatment-related variables on outcome and toxicity occurrence. Results: Seventy-two patients were treated to a median biologically effective dose (BED) of 105 (75–132) Gy10 . Two-year LC, DMFS, PFS, and OS were 83%, 46%, 43%, and 49%. BED>75 Gy10 was correlated to superior LC (p = 0.02), PFS (p = 0.036), and OS (p < 0.001). Grade ≥3 toxicity rate was 7%, including one fatal esophagitis. No variables were correlated to DMFS or to occurrence of overall and grade ≥3 toxicity. Conclusions: SBRT using dose-intensive schedules improves outcome in NSCLC patients. Overall toxicity is acceptable, although rare but potentially fatal toxicities may occur

Stereotactic Ablative Radiotherapy (SABR) in inoperable oligometastatic disease from colorectal cancer: a safe and effective approach

Background: To assess the safety and efficacy of Stereotactic Ablative Radiotherapy (SABR) in oligometastatic patients from colorectal cancer. Methods: 82 patients with 1-3 inoperable metastases confined to one organ (liver or lung), were treated with SABR for a total of 112 lesions in an observational study. Prescription dose ranged between 48 and 75Gy in 3 or 4 consecutive fractions. Primary end-points were local control (LC), overall survival (OS) and progression-free survival (PFS). Secondary end-point was toxicity. Results: Median follow-up was 24 months (range 3-47). One, two and three years LC rate was 90%,80% and 75% (85%,75% and 70% for lung and 95%, 90% and 85% for liver metastases; no statistically significance was found). The difference in LC between the subgroup of lesions treated with >= 60 Gy (n = 58) and those irradiated with 3 cm (p 3 toxicity. Conclusions: SABR is a safe and feasible alternative treatment of oligometastatic colorectal liver and lung metastases in patients not amenable to surgery or other ablative treatments

Critical appraisal of the potential role of intensity modulated proton therapy in the hypofractionated treatment of advanced hepatocellular carcinoma.

PURPOSE:To investigate the role of intensity modulated proton therapy (IMPT) for advanced hepatocellular carcinoma in comparison with volumetric modulated arc therapy (VMAT). METHODS:An in-silico planning study was performed on 20 patients. The prescription dose was 60Gy in 6 fractions. Patients were planned with abdominal compression. IMPT plans were optimized with or without the inclusion of CT calibration (3%) and isocenter positioning (2,4,6mm) uncertainties. Plan robustness was appraised comparing rubust optimized plans vs standard plans and also in terms of the worst-case scenario. VMAT plans were optimized for 10FFF photon beams using 2 partial arcs. RESULTS:Target coverage was fully achieved by both VMAT and IMPT plans with a significant improvement in homogeneity (~25%) with IMPT. Integral dose was reduced of ~60% with IMPT while the conformality of the dose distributions was similar among techniques. The sparing of the organs at risk was strongly improved with IMPT although all clinical objectives were met for both techniques. The inclusion of the uncertainties in the optimization lead to some deterioration in the target dose homogeneity (from 40 to 80% worse with 4 or 6mm position uncertainty) while none of the coverage parameters or OAR objective was violated. The worst-case scenario analysis demonstrated the risk of a major target underdosage only in the case of the most extreme errors (6mm) with D98% in average ~12% lower than the threshold. CONCLUSION:IMPT with the support of abdominal compression, can be considered a viable solution also for advanced hepatocellular carcinoma patients. Great care shall be put in the minimization of the residual respiration and positioning uncertainties but the dosimetric advantage for organs at risk and the relative robustness on target coverage are promising factors

New Perspectives in the Treatment of Colorectal Metastases

Background: In recent years, the management of metastatic colorectal cancer has become more aggressive and more multidisciplinary. New treatment options have been proposed in addition to the standard approach of resection of liver metastases and chemotherapy.Summary: Selected patients with synchronous limited peritoneal and liver disease (perito-neal cancer index <12 and <3 liver metastases) can be scheduled for aggressive treatment, including cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, and liver re-section. This approach has achieved survival benefits, even if the treatment is unlikely to be curative in most patients. Moreover, liver transplantation has been recently reconsidered for liver-only metastases, resulting in the de facto reinstatement of the chance of surgery for some unresectable patients. Even though indications for liver transplantation remain to be standardized, preliminary studies have reported extremely promising outcomes. Radio-embolization has proven to be an effective additional tool for the treatment of unresect-able tumors, and its potential role in association with chemotherapy for resectable disease is currently being investigated. Stereotactic body radiation therapy is a safe, non-invasive, and effective therapeutic option for patients with inoperable oligometastatic disease. Thanks to recent technical progress, high radiation doses can now be delivered in fewer fractions with excellent local disease control and a low risk of radiation-induced liver injury. Finally, radiofrequency ablation (RFA) for colorectal metastases has become more effective, with results approaching those of surgical series. New interstitial treatments, such as microwave ablation and irreversible electroporation, could overcome some of the limitations of RFA, thereby further expanding indications and optimizing outcomes. Key Messages: Currently, a multidisciplinary approach to patients with colorectal liver metastases is mandatory. Aggres-sive surgical treatments should be integrated with all the available non-surgical options to maximize disease control and patient survival

Oligoscore: a clinical score to predict overall survival in patients with oligometastatic disease treated with stereotactic body radiotherapy

Background to find clinical features that can predict prognosis in patients with oligometastatic disease treated with stereotactic body radiotherapy (SBRT) Material and methods Patients with less than 5 metastases in less than 3 different body sites were included in the analysis. Various clinical and treatment parameters were analyzed to create a Cox proportional hazard model for Overall Survival (OS). Subsequently, significant variables were used to create a score Results 997 patients were analyzed. Median OS was 2.61 years, 1 and 3 years OS was respectively 85% and 43%. Location of the primary tumor, performance status, site of irradiated metastases, presence of extratarget non irradiated lesions and RT dose were significant prognostic factors for OS. These parameters were used to create a score and to distinguish three different classes, with median OS of 5.67 years in low risk, 2.47 years in intermediate risk and 1.82 years in high risk group. Conclusion moving from easily accessible clinical parameters, a score was created to help the physician's decision about the better treatment or combination of treatments for the individual patient

The role of SBRT in oligometastatic patients with liver metastases from breast cancer

Liver metastases from breast cancer are a common occurrence. Local ablative therapies are a promising therapeutic option for these patients, with the potential for a long term disease control in the setting of “oligometastatic patients”. Identification of the perfect candidate for local approaches is still challenging and unclear. Stereotactic body radiation therapy (SBRT) is one of the most valuable local therapy, because of great efficiency, low morbidity and minimal invasiveness. In this paper, we reviewed the state of the art in the care of breast cancer patients with liver metastases, with a focus on SBRT

Dosimetric impact of volumetric modulated arc therapy for nasopharyngeal cancer treatment

Background: The purpose of the study was to evaluate the toxicity and outcome of nasopharyngeal carcinoma patients treated using 3-dimensional conformal radiotherapy (3DCRT) or volumetric modulated arc therapy (VMAT) technique. Materials and methods: 68 patients treated between 2006 and 2018 were retrospectively analysed. Since 2009 patients received 3DCRT with 50/70 Gy to the elective/boost volumes in 35 fractions; from then, VMAT with simultaneous integrated boost (SIB) with 54.45/69.96 Gy in 33, or 54/66 Gy in 30 fractions. Induction chemotherapy was administered in 74% of the patients, concomitant cisplatinum in 87%. Acute and late toxicity data, progression-free survival PSF and overall survival OS, and toxicity correlations with dose metrics were reported. Results: With a median follow-up of 64 months, complete remission at the last evaluation was in 68% of the patients, while 28% and 9% had locoregional relapse and distant disease, respectively. The 5- and 10-year progression free survival (PFS) rates were 62.7±6.5% and 53.2±8.7%, respectively. The 5- and 10-year OS rates were 78.9 ± 5.5% and 61.4 ± 9.2%, respectively. At the multivariate Cox analysis TNM stage (p = 0.02) and concomitant chemotherapy (p = 0.01) resulted significant for PFS, concomitant chemotherapy (p = 0.04) for OS. Improvements in acute toxicity were presented for VMAT patients due to its ability to spare OARs. Odds ratio (OR) for acute salivary toxicity, between VMAT and 3DCRT, was 4.67 (p = 0.02). Dosimetrically, salivary toxicity correlated with mean parotid dose (p = 0.05), dysphagia with laryngeal (p = 0.04) and mean oral cavity (p = 0.06) doses, when dose-volume histograms (DVHs) are corrected for fractionation. Conclusion: This study is a proof of a significant benefit of the VMAT technique compared with 3DCRT in terms of side effects in nasopharynx patients, and adds dosimetric correlations