Actuarial Local Control Rate Research Articles

Clinical Outcomes Following Dose-Escalated Proton Therapy for Skull-Base Chordoma.

PurposeTo evaluate the effectiveness of external-beam proton therapy (PT) on local control and survival in patients with skull-base chordoma.Materials and MethodsWe reviewed the medical records of patients with skull-base chordoma treated with definitive or adjuvant high-dose PT and updated their follow-up when feasible. We assessed overall survival, disease-specific survival, local control, and freedom from distant metastasis. Radiotherapy toxicities were scored using the Common Terminology Criteria for Adverse Events, version 4.0.ResultsA total 112 patients were analyzed, of whom 105 (94%) received PT and 7 (6%) received combined proton-photon therapy between 2007 and 2019. Eighty-seven patients (78%) underwent a subtotal resection, 22 (20%) a gross total resection, and 3 (3%) a biopsy alone. The median radiotherapy dose was 73.8 Gy radiobiologic equivalent (GyRBE; range, 69.6-74.4). Ninety patients (80%) had gross disease at radiotherapy and 7 (6%) were treated for locally recurrent disease following surgery. Median follow-up was 4.4 years (range, 0.4-12.6); for living patients, it was 4.6 years (range, 0.4-12.6), and for deceased patients, 4.1 years (range, 1.2-11.2). At 5 years after radiotherapy, the actuarial overall survival, disease-specific survival, local control, and freedom from distant metastasis rates were 78% (n = 87), 83% (n = 93), 74% (n = 83), and 99% (n = 111), respectively. The median time to local progression was 2.4 years (range, 0.8-7). Local control and disease-specific survival by resection status was 95% versus 70% (P = 0.28) and 100% versus 80% (P = 0.06) for gross total, versus subtotal, resection or biopsy alone, respectively. There were no serious acute toxicities (grade ≥ 3) related to radiotherapy.ConclusionHigh-dose PT alone or after surgical resection for skull-base chordoma reaffirms the favorable 5-year actuarial local control rate compared with conventional techniques with acceptable late-complication–free survival. Outcomes following gross total resection and adjuvant PT were excellent. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.

Single-fraction versus hypofractionated gamma knife radiosurgery for small metastatic brain tumors.

Stereotactic radiosurgery (SRS) has become a standard of care for the treatment of metastatic brain tumors (METs). Although a better balance of tumor control and toxicity of hypofractionated SRS (hfSRS) compared with single-fraction SRS (sfSRS) was demonstrated in large METs, there is no data comparing two approaches for small METs (< 4 cm3). It was aimed to compare clinical outcomes between sfSRS versus hfSRS Gamma Knife radiosurgery (GKRS) in a series of patients with unresected, small METs. Patients (n = 208) treated with sfGKRS or hfGKRS between June 2017 and May 2020 were retrospectively examined in a single center. The co-primary endpoints of local control (LC) and toxicity were estimated by applying the Kaplan-Meier method. Multivariate analysis using Cox proportional hazards (HR) modeling was used to assess the effect of independent variables on the outcomes. The actuarial LC rate was 99.7% at six months and 98.8% at 18months in the sfGKRS group, and 99.4% and 94.3% in the hfGKRS group (p = 0.089), respectively. In multivariate analysis, MET volume (p = 0.023, HR 2.064) and biologically effective dose (BED10) (p < 0.0001, HR 0.753) was associated with LC. In total, treatment-related toxicity was observed in 13 (8.7%) patients during a median period of 10weeks (range 1-31). Radiation necrosis was observed in four patients (1.9%), and all patients were in the sfGKRS group (p = 0.042). Only the maximum dose was associated with toxicity (p = 0.032, HR 1.047). Our current results suggest that hfGKRS is advantageous and beneficial also in patients with unresected, small METs.

Chemoradiotherapy by intensity-modulated radiation therapy with simultaneous integrated boost in locally advanced or oligometastatic non-small-cell lung cancer\u2014a\xa0two center experience

PurposeIntegrating moderate hypofractionation to the macroscopic tumor with elective nodal irradiation while sparing the organs at risk (OAR) in chemoradiotherapy of locally advanced non-small-cell lung cancer.MethodsFrom 2010–2018, treatment, patient and tumor characteristics of 138 patients from two radiation therapy centers were assessed. Chemoradiotherapy by intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) to the primary tumor and macroscopic lymph node metastases was used.ResultsA total of 124 (90%) patients received concurrent chemotherapy. 106 (76%) patients had UICC (Union for International Cancer Control) stage ≥IIIB and 21 (15%) patients had an oligometastatic disease (UICC stage IV). Median SIB and elective total dose was 61.6 and 50.4 Gy in 28 fractions, respectively. Furthermore, 64 patients (46%) had an additional sequential boost to the primary tumor after the SIB-IMRT main series: median 6.6 Gy in median 3 fractions. The median cumulative mean lung dose was 15.6 Gy (range 6.2–29.5 Gy). Median follow-up and radiological follow-up for all patients was 18.0 months (range 0.6–86.9) and 16.0 months (range 0.2–86.9), respectively. Actuarial local control rates at 1, 2 and 3 years were 80.4, 68.4 and 57.8%. Median overall survival and progression-free survival was 30.0 months (95% confidence interval [CI] 23.5–36.4) and 12.1 months (95% CI 8.2–16.0), respectively. Treatment-related toxicity was moderate. Radiation-induced pneumonitis grade 2 and grade 3 occurred in 13 (9.8%) and 3 (2.3%) patients.ConclusionsChemoradiotherapy using SIB-IMRT showed promising local tumor control rates and acceptable toxicity in patients with locally advanced and in part oligometastatic lung cancer. The SIB concept, resulting in a relatively low mean lung dose, was associated with low numbers of clinically relevant pneumonitis. The overall survival appears promising in the presence of a majority of patients with UICC stage ≥IIIB disease.

Clinical Outcomes of Patients With pT1-T2N0 Oral Tongue Squamous Cell Carcinoma.

The objective of this study was to evaluate the clinical outcomes in a cohort of patients with early-stage oral tongue squamous cell carcinoma (OTSCC). We conducted a retrospective analysis of patients with pT1-T2N0 (American Joint Committee on Cancer [AJCC] seventh edition) OTSCC treated from 2000 to 2018. Two-year actuarial rates of local regional control, cancer-specific survival, and overall survival were calculated for the entire cohort and patients with/without adjuvant radiation. Ninety-six patients met the criteria with a median follow-up of 4 years; 14 had adjuvant radiation, while 82 had surgery alone. Two-year local regional control was 82.7% (75.4% to 90.8%) for the entire cohort, 84.9% (77.8% to 93.2%) for surgery only, and 70.7% (50.2% to 99.6%) for patients with adjuvant radiation. Two-year progression-free survival was 82.7% (75.3% to 90.8%). Of the 20 patients with recurrence, 11 (55%) were successfully salvaged. Local regional recurrence remains modest in early-stage OTSCC, but salvage is possible with high survival rates. Level III-retrospective cohort study.

Cyberknife\xae hypofractionated stereotactic radiosurgery (CK-hSRS) as salvage treatment for brain metastases

PurposeThe introduction of hypofractionated stereotactic radiosurgery (hSRS) extended the treatment modalities beyond the well-established single-fraction stereotactic radiosurgery and fractionated radiotherapy. Here, we report the efficacy and side effects of hSRS using Cyberknife® (CK-hSRS) for the treatment of patients with critical brain metastases (BM) and a very poor prognosis. We discuss our experience in light of current literature.MethodsAll patients who underwent CK-hSRS over 3 years were retrospectively included. We applied a surface dose of 27 Gy in 3 fractions. Rates of local control (LC), systemic progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan–Meier method. Treatment-related complications were rated using the Common Terminology Criteria for Adverse Events (CTCAE).ResultsWe analyzed 34 patients with 75 BM. 53% of the patients had a large tumor, tumor location was eloquent in 32%, and deep seated in 15%. 36% of tumors were recurrent after previous irradiation. The median Karnofsky Performance Status was 65%.The actuarial rates of LC at 3, 6, and 12 months were 98%, 98%, and 78.6%, respectively.Three, 6, and 12 months PFS was 38%, 32%, and 15%, and OS was 65%, 47%, and 28%, respectively. Median OS was significantly associated with higher KPS, which was the only significant factor for survival. Complications CTCAE grade 1–3 were observed in 12%.ConclusionOur radiation schedule showed a reasonable treatment effectiveness and tolerance. Representing an optimal salvage treatment for critical BM in patients with a very poor prognosis and clinical performance state, CK-hSRS may close the gap between surgery, stereotactic radiosurgery, conventional radiotherapy, and palliative care.

Stereotactic Ablative Radiation Therapy to All Lesions in Patients With Oligometastatic Cancers: A Phase 1 Dose-Escalation Trial

Increasing evidence suggests that patients with a limited number of metastases benefit from SABR to all lesions. However, the optimal dose and fractionation remain unknown. This is particularly true for bone and lymph node metastases. Therefore, a prospective, single-center, dose-escalation trial was initiated. Dose-Escalation trial of STereotactic ablative body RadiOtherapY for non-spine bone and lymph node metastases (DESTROY) was an open-label phase 1 trial evaluating SABR to nonspine bone and lymph node lesions in patients with up to 3 metastases. Patients with European Cooperative Oncology Group performance status ≤1, an estimated life expectancy of at least 6 months, and histologically confirmed nonhematological malignancy were eligible. Three SABR fractionation regimens, ie, 5 fractions of 7.0 Gy versus 3 fractions of 10.0 Gy versus a single fraction of 20.0 Gy, were applied in 3 consecutive patient cohorts. The rate of ≥grade 3 toxicity, scored according to the Common Toxicity Criteria for Adverse Events v. 4.03, up to 6 months after SABR, was the primary endpoint. The trial was registered on clinicaltrials.gov (NCT03486431). Between July 2017 and December 2018, 90 patients were enrolled. In total 101 metastases were treated. No ≥grade 3 toxicity was observed in any of the enrolled patients (95% CI 0.0%-12.3% for the first cohort with 28 analyzable patients; 95% CI 0.0%-11.6% for the second and third cohort with 30 analyzable patients each). Treatment-related grade 2 toxicities occurred in 4 out of 30 versus 2 out of 30 versus 2 out of 30 patients for the 5, 3 and 1 fraction schedule, respectively. Actuarial local control rate at 12 months was 94.5%. All 3 treatment schedules were feasible and effective with remarkably low toxicity rates and high local control rates. From a patient and resource point of view, the single-fraction schedule is undoubtedly most convenient.

Outcomes following limited-volume proton therapy for multifocal spinal myxopapillary ependymoma.

Spinal myxopapillary ependymoma (MPE) often presents with a multifocal distribution, complicating attempts at resection. There remains no standard approach to irradiating these patients. We report disease control and toxicity in pediatric patients with multifocal spinal MPE treated with limited-volume proton therapy. Twelve patients (≤21 years old) with multifocal spinal MPE were treated between 2009 and 2018 with limited-volume brain-sparing proton therapy. Median age was 13.5 years (range, 7-21). Radiotherapy was given as adjuvant therapy after primary surgery in five patients (42%) and for recurrence in seven (58%). No patient received prior radiation. Eleven patients (92%) had evidence of gross disease at radiotherapy. Eleven patients received 54 GyRBE; one received 50.4 GyRBE. Treatment toxicity was graded per the CTCAEv4.0. We estimated disease control and survival using the Kaplan-Meier product-limit method. The median follow-up was 3.6 years (range, 1.8-10.6). The five-year actuarial rates of local control, progression-free survival, and overall survival were 100%, 92%, and 100%, respectively. One patient experienced an out-of-field recurrence in the spine superior to the irradiated region. No patients developed in-field recurrences. Following surgery and irradiation, one patient developed grade three spinal kyphosis and one patient developed grade 2 unilateral L5 neuropathy. 54 GyRBE to a limited volume appears effective for disseminated spinal MPE in both the primary and salvage settings, sparing children the toxicity of full craniospinal irradiation. Compared with historical reports, this approach using proton therapy improves the therapeutic ratio, resulting in minimal side effects and high rates of disease control.

Treatment of intracranial meningioma with single-session and fractionated radiosurgery: a propensity score matching study

Single-session stereotactic radiosurgery (SSRS) is recognized as a safe and efficient treatment for meningioma. We aim to compare the long-term efficacy and safety of fractionated stereotactic radiotherapy (FSRT) with SSRS in the treatment of grade I meningioma. A total of 228 patients with 245 tumors treated with radiosurgery between March 2006 and June 2017were retrospectively evaluated. Of these, 147 (64.5%) patients were treated with SSRS. The remaining 81 patients (35.5%) were treated with a fractionated technique. Protocols to treat meningioma were classified as 12–16 Gy per fraction for SSRS and 7 Gy/fraction/day for three consecutive days to reach a total dose of 21 Gy for FSRT. In univariate and multivariate analyses, tumor volume was found to be associated with local control rate (hazard ratio = 4.98, p = 0.025). The difference in actuarial local control rate (LCR) between the SSRS and FSRT groups after propensity score matching (PSM) was not statistically significant during the 2-year (96.86% versus 100.00%, respectively; p = 0.175), 5-year (94.76% versus 97.56%, respectively; p = 0.373), and 10-year (74.40% versus 91.46%, respectively; p = 0.204) follow-up period. FSRT and SSRS were equally well-tolerated and effective for the treatment of intracranial benign meningioma during the10-year follow-up period.

Imaging-Based Local Control Outcomes Specific To Spine Stereotactic Body Radiotherapy (SBRT) For Prostate Cancer Metastases

We report the first dedicated series of spine SBRT specific to prostate cancer metastases. A prospective database was retrospectively reviewed identifying 183 spinal segments in 93 prostate cancer patients treated with SBRT. All patients were followed regularly post-SBRT with both a clinical exam and full spine MRI. The primary endpoint was imaging-based local control rates and secondary outcomes included overall survival (OS) and vertebral compression fracture (VCF). Of the 183 treated spine segments, 130 (71%) had no prior radiation, 18 (10%) were post-operative, and 35 (19%) were re-irradiated after conventional RT. The median follow-up was 16 months (range 2-70 months). 67 patients were oligometastatic (<5 metastases) of which 36 had a solitary spinal metastasis. 44 patients (47%) had castrate resistant disease at the time of SBRT, while 10 of the 49 patients with hormone sensitive disease at the time of SBRT developed castrate resistance during follow up at a median time of 15 months after SBRT (range 7 – 37 months). Of the 183 spinal lesions, 120 (65%) were sclerotic, 32 (18%) were lytic, and 31 (17%) were mixed. The median spinal instability neoplastic score (SINS) was 5 (range 0-13). The majority of spinal segments (75%) were treated with 24-28 Gy/2 fractions while the rest (25%) were treated with 25-30 Gy/4-5 fractions. Actuarial local control (LC) rates at 1 and 2 years were 97% and 92%, respectively. The median OS was 61 months (range 43-77 months) and the 1- and 2-year OS rates were 91% and 81%, respectively. The cumulative risk of VCF was 5% at 1-year and 13% at 2 years. Excellent local control rates were observed in this cohort of patients with spinal metastases from prostate cancer with an acceptable risk of VCF. The high rate of OS in prostate cancer supports the need for excellent LC of spinal disease. Whether similar rates could be observed with conventional palliative radiation remains to be proven. Further work will identify predictive factors for local control and fracture rate after SBRT.

Correlation of clinical outcome, radiobiological modeling of tumor control, normal tissue complication probability in lung cancer patients treated with SBRT using Monte Carlo calculation algorithm.

Purpose/BackgroundWe analyzed the predictive value of non‐x‐ray voxel Monte Carlo (XVMC)‐based modeling of tumor control probability (TCP) and normal tissue complication probability (NTCP) in patients treated with stereotactic body radiotherapy (SBRT) using the XVMC dose calculation algorithm.Materials/MethodsWe conducted an IRB‐approved retrospective analysis in patients with lung tumors treated with XVMC‐based lung SBRT. For TCP, we utilized tumor size‐adjusted biological effective dose (s‐BED) TCP modeling validated in non‐MC dose calculated SBRT to: (1) verify modeling as a function of s‐BED in patients treated with XVMC‐based SBRT; and (2) evaluate the predictive potential of different PTV dosimetric parameters (mean dose, minimum dose, max dose, prescription dose, D95, D98, and D99) for incorporation into the TCP model. Correlation between observed local control and TCPs was assessed by Pearson's correlation coefficient. For NTCP, Lyman NTCP Model was utilized to predict grade 2 pneumonitis and rib fracture.ResultsEighty‐four patients with 109 lung tumors were treated with XVMC‐based SBRT to total doses of 40 to 60 Gy in 3 to 5 fractions. Median follow‐up was 17 months. The 2‐year local and local‐regional control rates were 91% and and 78%, respectievly. All estimated TCPs correlated significantly with 2‐year actuarial local control rates (P < 0.05). Significant corelations between TCPs and tumor control rate according to PTV dosimetric parameters were observed. D99 parameterization demonstrated the most robust correlation between observed and predicted tumor control. The incidences of grade 2 pneumonitis and rib fracture vs. predicted were 1% vs. 3% and 10% vs. 13%, respectively.ConclusionOur TCP results using a XVMC‐based dose calculation algorithm are encouraging and yield validation to previously described TCP models using non‐XVMC dose methods. Furthermore, D99 as potential predictive parameter in the TCP model demonstrated better correlation with clinical outcome.

Pre-stereotactic radiosurgery neutrophil-to-lymphocyte ratio is a predictor of the prognosis for brain metastases.

The neutrophil-to-lymphocyte ratio (NLR) has been reported to relate to the prognosis of various cancers. The aim of this study was to elucidate the efficiency of pre-treatment NLR as a predictor of outcomes of brain metastasis underwent gamma knife radiosurgery (GKRS). We analyzed 195 cases with brain metastasis underwent GKRS at our institution between January 2015 and April 2018. Patients' clinical and radiographic data were collected. We identified 458 brain metastases in 195 patients. Optimal dichotomous cutoff values of NLR determined by receiver operating characteristic analysis for local control, distant control and overall survival (OS) were 2.48, 2.74 and 3.13, respectively. The actuarial local control rates of patients with high NLR were 87.4% at 6months and 76.1% at 12months, whereas that of patients with low NLR were 94.2% at 6months and 88.3% at 12months (P = 0.001). The actuarial distant control rates of patients with high NLR were 31.4% at 6months and 18.9% at 12months, whereas that of patients with low NLR were 58.5% at 6months and 31.3% at 12months (P = 0.001). The median OS of patients with high and low NLR were 10.0months and 14.5months, respectively (P = 0.001). Multivariate analysis demonstrates that high NLR independently predicts local failure (hazard ratio [HR], 2.281; P = 0.003), distant brain failure (HR 1.775; P = 0.002) and poorer overall survival (HR 1.494; P = 0.034). The pre-SRS NLR, a systemic inflammatory marker for treatment response, inversely predicts local control, distant control and OS in patients with brain metastasis.

Single-fraction radiosurgery versus fractionated stereotactic radiotherapy in patients with brain metastases: a comparative study

To compare the local control and brain radionecrosis in patients with brain metastasis primarily treated by single-fraction radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (HFSRT). Between January 2012 and December 2017, 179 patients with only 1-3 brain metastases (total: 287) primarily treated by SRS (14Gy) or HFSRT (23.1Gy in 3 fractions of 7.7Gy, every other day) were retrospectively analyzed in a single center. Follow-up imaging data were available in 152 patients with 246 lesions. The corresponding Biological Effective Dose (BED) were 33.6Gy and 40.9Gy respectively for SRS and HFSRT group, assuming an α/β of 10Gy. Local control (LC) and risk of radionecrosis (RN) were calculated by the Kaplan-Meier method. The actuarial local control rates at 6 and 12months were 94% and 88.1% in SRS group, and 87.6% and 78.4%, in HFSRT group (p = 0.06), respectively. Only the total volume of edema was associated with worse LC (p = 0.01, HR 1.02, 95% CI [1.004-1.03]) in multivariate analysis. Brain radionecrosis occurred in 1 lesion in SRS group and 9 in HFSRT group. Median time to necrosis was 5.5months (range 1-9). Only the volume of GTV was associated with RN (p = 0.02, HR 1.09, 95% CI [1.01-1.18]) in multivariate analysis. Multi-fraction SRT dose of 23.31Gy in 3 fractions has similar efficacy to single-fraction SRT dose of 14Gy in patients with brain metastases. A slightly higher occurrence of radionecrosis appeared in HFSRT group.

Correlating Dose Variables with Local Tumor Control in Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer: A Modeling Study on 1500 Individual Treatments

Large variation regarding prescription and dose inhomogeneity exists in stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer. The aim of this modeling study was to identify which dose metric correlates best with local tumor control probability to make recommendations regarding SBRT prescription. We combined 2 retrospective databases of patients with non-small cell lung cancer, yielding 1500 SBRT treatments for analysis. Three dose parameters were converted to biologically effective doses (BEDs): (1) the (near-minimum) dose prescribed to the planning target volume (PTV) periphery (yielding BEDmin); (2) the (near-maximum) dose absorbed by 1% of the PTV (yielding BEDmax); and (3) the average between near-minimum and near-maximum doses (yielding BEDave). These BED parameters were then correlated to the risk of local recurrence through Cox regression. Furthermore, BED-based prediction of local recurrence was attempted by logistic regression and fast and frugal trees. Models were compared using the Akaike information criterion. There were 1500 treatments in 1434 patients; 117 tumors recurred locally. Actuarial local control rates at 12 and 36 months were 96.8% (95% confidence interval, 95.8%-97.8%) and 89.0% (87.0%-91.1%), respectively. In univariable Cox regression, BEDave was the best predictor of risk of local recurrence, and a model based on BEDmin had substantially less evidential support. In univariable logistic regression, the model based on BEDave also performed best. Multivariable classification using fast and frugal trees revealed BEDmax to be the most important predictor, followed by BEDave. BEDave was generally better correlated with tumor control probability than either BEDmax or BEDmin. Because the average between near-minimum and near-maximum doses was highly correlated to the mean gross tumor volume dose, the latter may be used as a prescription target. More emphasis could be placed on achieving sufficiently high mean doses within the gross tumor volume rather than the PTV covering dose, a concept needing further validation.

High-dose-rate brachytherapy using Leipzig applicators for non-melanoma localized skin cancer.

PurposeTechnological advances with commercial production of surface applicators allowed high-dose-rate (HDR) afterloading brachytherapy to overpass challenges associated with the delivery of superficial radiation when treating non-melanoma skin cancer (NMSC). We reviewed our single institutional experience using HDR to treat basal (BCC) and squamous cell (SCC) carcinomas.Material and methodsA retrospective review of all patients treated with HDR and Leipzig-style applicators for NMSC at the Radiation Oncology Department, AC Camargo Cancer Center, from March 2013 to December 2018 was performed.ResultsSeventy-one patients with 101 lesions (BCCs, 69.3% or n = 70) and median age 80 (range, 51-102) years old were evaluated. The median follow-up was 42.8 (range, 12-82) months. The 3-year and 5-year actuarial local control (LC) rates were 97.9% and 87.2%, respectively. On univariate analysis, treatments with EQD2 less than 50 Gy (p < 0.001) and dose per fraction smaller than 3 Gy (p < 0.001) were found to be statistically significant predictive factors of a worse outcome. On multivariate analysis, SCC had a worse prognosis over BCC (p = 0.007, HR = 2.3, CI: 1.2-6.6). All patients developed some degree of acute side effects graded 1 to 2. Grade 3 acute side effects were observed in 9 (8.9%) patients. Moreover, severe late side effects (grade 3), hypopigmentation, and telangiectasia were observed in 4 (3.9%) patients. No grade 4 acute or late side effects were seen in this cohort.ConclusionsHDR offers a convenient treatment schedule for patients and is associated with excellent LC. The most effective regimen, in terms of dose and fractionation, to treat superficial NMSC with HDR remains uncertain, but a moderate minimum EQD2 dose of 50 Gy should be used.

Radiotherapy in the treatment of extracranial hemangiopericytoma/solitary fibrous tumor: Study from the Rare Cancer Network

Background and purposeThe role of radiotherapy (RT) in the treatment of hemangiopericytoma/solitary fibrous tumor (HPC/SFT) is still under debate. We aimed at investigating whether radiotherapy can improve the results in patients operated for extracranial HPC/SFT. Materials and methodsData from patients with HPC/SFT, treated from 1982 to 2012, were retrospectively reviewed within the Rare Cancer Network framework. Actuarial local control (LC), disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS) were calculated with Kaplan-Meyer method. Patient and tumor parameters were analyzed by univariate and multivariate analysis. ResultsOf 114 HPC/SFT, 58 (50.9%) occurred in the extremities/superficial trunk and 56 (49.1%) in intra-thoracic/retroperitoneum. Seventy-eight patients (68.4%) underwent surgery only (Sx), and 36 (31.6%) Sx and RT (Sx + RT). Median RT dose was 60 Gy (range 45–68.4 Gy) in 1.6–2.2 Gy fractions. In the extremities/superficial trunk group of patients, actuarial 5-year LC rates were 50.4% after Sx and 91.6% after Sx + RT (p < 0.0001) for LC, and 50.4% after Sx and 83.1% after Sx + RT (p = 0.008) for DFS. In the intra-thoracic/retroperitoneum group of patients, actuarial 5-year rates were 89.3% after Sx and 77.8% after Sx + RT (p = 0.99) for LC, and 73.8% after Sx and 77.8% after Sx + RT (p = 0.93) for DFS. At multivariate analysis, the addition of RT resulted in better LC and DFS in the whole series. The advantage was confirmed for LC in the group of patients affected by extremity/superficial trunk tumors. ConclusionAddition of RT to Sx could improve the prognosis, in terms of LC and DFS, essentially in patients with extremities/superficial trunk tumor locations.

Proceedings to the 6th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA): 14-16 October 2019, Hosted by Miami Cancer Institute, part of Baptist Health South Florida, Miami, FL, USA.

Proceedings to the 6th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA): 14-16 October 2019, Hosted by Miami Cancer Institute, part of Baptist Health South Florida, Miami, FL, USA.

RARE-40. OUTCOMES AFTER PROTON THERAPY FOR SKULL-BASE CHORDOMA: A PROSPECTIVE STUDY

Abstract We evaluated treatment outcomes following definitive or adjuvant high-dose, image-guided proton therapy in 91 patients with skull-base chordoma enrolled on a prospective outcomes tracking protocol and treated between February 2007 and February 2018. The median age was 53 years (range, 22–78 years). Patients received passively scattered 3-dimensional conformal proton therapy to a median dose of 73.8 GyRBE (range, 69.6–75.6 GyRBE). Two patients received a component of intensity-modulated radiotherapy. Seventy percent (n=64) were men and 30% (n=27) were woman. Eighty-two percent (n=75) of patients had macroscopic disease at the time of radiotherapy; 18% (n=16) had undergone a macroscopic gross total resection. Overall survival, cause-specific survival, local control, and RT-related grade 3 toxicity-free survival were calculated. Proton therapy-related toxicities were scored using CTCAE v4.0. With a median follow-up of 3.7 years (range, 0.2–10 years), 26 patients experienced disease recurrence, including 26 local, 0 regional, and 1 distant recurrence. The median time to local progression was 2.2 years (range, 0.4–7.0 years). At the time of last follow-up, 66 patients were alive (56 with no evidence of disease progression) and 25 were deceased (18 with disease progression). There were no acute grade 3 toxicities related to the radiation therapy. The 4-year actuarial rates of overall survival, cause-specific survival, local control, and radiation therapy-related grade 3 toxicity-free survival were 83%, 87%, 76% and 83%, respectively. Definitive or adjuvant high-dose passively scattered 3-dimensional conformal proton therapy for skull-base chordoma provides acceptable local control, comparing favorably to historic photon data, with no acute grade ≥3 radiation-related toxicity and an acceptable rate of grade ≥3 late toxicity. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.

A Large, Multicenter, Retrospective Study on Efficacy and Safety of Stereotactic Body Radiotherapy (SBRT) in Oligometastatic Ovarian Cancer (MITO RT1 Study): A Collaboration of MITO, AIRO GYN, and MaNGO Groups.

Recent studies have reported improvement of outcomes (progression-free survival, overall survival, and prolongation of androgen deprivation treatment-free survival) with stereotactic body radiotherapy (SBRT) in non-small cell lung cancer and prostate cancer. The aim of this retrospective, multicenter study (MITO RT-01) was to define activity and safety of SBRT in a very large, real-world data set of patients with metastatic, persistent, and recurrent ovarian cancer (MPR-OC). The endpoints of the study were the rate of complete response (CR) to SBRT and the 24-month actuarial local control (LC) rate on "per-lesion" basis. The secondary endpoints were acute and late toxicities and the 24-month actuarial late toxicity-free survival. Objective response rate (ORR) included CR and partial response (PR). Clinical benefit (CB) included ORR and stable disease (SD). Toxicity was evaluated by the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) and Common Terminology Criteria for Adverse Events (CTCAE) scales, according to center policy. Logistic and Cox regression were used for the uni- and multivariate analysis of factors predicting clinical CR and actuarial outcomes. CR, PR, and SD were observed in 291 (65.2%), 106 (23.8%), and 33 (7.4%) lesions, giving a rate of CB of 96.4%. Patient aged ≤60 years, planning target volume (PTV) ≤18 cm3 , lymph node disease, and biologically effective dose α/β10 > 70 Gy were associated with higher chance of CR in the multivariate analysis. With a median follow-up of 22 months (range, 3-120), the 24-month actuarial LC rate was 81.9%. Achievement of CR and total dose >25 Gy were associated with better LC rate in the multivariate analysis. Mild toxicity was experienced in 54 (20.7%) patients; of 63 side effects, 48 were grade 1, and 15 were grade 2. The 24-month late toxicity-free survival rate was 95.1%. This study confirms the activity and safety of SBRT in patients with MPR-OC and identifies clinical and treatment parameters able to predict CR and LC rate. This study aimed to define activity and safety of stereotactic body radiotherapy (SBRT) in a very large, real life data set of patients with metastatic, persistent, recurrent ovarian cancer (MPR-OC). Patient age <60 years, PTV <18 cm3 , lymph node disease, and biologically effective dose α/β10 >70 Gy were associated with higher chance of complete response (CR). Achievement of CR and total dose >25 Gy were associated with better local control (LC) rate. Mild toxicity was experienced in 20.7% of patients. In conclusion, this study confirms the activity and safety of SBRT in MPR-OC patients and identifies clinical and treatment parameters able to predict CR and LC rate.

Local Regional Recurrence rates for pT1-2 N0 Oral Tongue Squamous Cell Carcinoma Treated with Surgery Alone at a High Volume Academic Multidisciplinary Head and Neck Oncology Program

To report the treatment outcomes of definitive surgery without adjuvant radiation or chemotherapy for patients with pT1-T2 N0 oral tongue squamous cell carcinoma (OTSCC). We conducted a retrospective analysis of patients with pT1-T2N0 (AJCC 7th edition) OTSCC treated at a single academic institution from 2008 to 2018. All patients had definitive surgery at one academic institution with no adjuvant treatment. Two year actuarial rates of local control (LC), regional control (RC), local regional control (LRC), cancer specific survival (CSS), and overall survival (OS) were calculated. Sixty six patients were included in this analysis. The median follow up was 33.9 months (1.2 – 121.8). When using updated staging, 61.5% had pT1 disease, 29.2% had pT2 disease, and 7.7% had pT3 disease (had been pT2 in 7th edition staging). Zero patients had positive margins, 27 had close margins, 1 had positive perineural invasion, 3 had positive LVI, and 18 had DOI > 4mm (13 patients did not have DOI information). Fourteen (14) patients had recurrence: 11 local and 7 regional (4 had both). The 2 year LC, RC, LRC, CSS, and OS were the following: 86%, 95%, 82%, 96%, and 96%. Of the patients with recurrence, 64% (9) were pT1, 21% (3) were pT2, and 14% (2) were pT3. The majority of the patients had elective neck dissection (50 patients, 76%) and specifically 71% of those who recurred had elective neck dissection. No pathological feature was found to be significantly correlated with recurrence. Salvage retreatment was successful for 9 of the 14 recurrences. Recurrence rates after surgery alone for patients with pT1-2N0 OTSCC treated at a high volume academic program are not insignificant (18%), however salvage retreatment is possible. It is reasonable to consider postoperative radiotherapy in patients with pT1-T2N0 OTSCC.

Usefulness of Stereotactic Body Radiation Therapy for Treatment of Adrenal Gland Metastases.

Purpose: This study aimed to describe our institutional experience in the use of stereotactic body radiation therapy (SBRT) for the management of adrenal gland metastases from multiple primary cancers.Materials and Methods: We retrospectively reviewed 31 patients who underwent SBRT as treatment for 33 adrenal gland lesions in the academic radiotherapy department of Oscar Lambret cancer center between May 2011 and September 2018. The primary study endpoints were 1- and 2-year local control rates, defined as the absence of progression at the treatment site based on the response evaluation criteria in solid tumors (RECIST). Toxicities were graded in accordance with the Common Terminology Criteria for Adverse Events version 4.03.Results: The average tumor volume was 33.5 cm3 (standard deviation: 51.7 cm3), and the prescribed dose ranged from 30 to 55 Gy given in 3–9 fractions. The median biological effective dose was 112.5 Gy (range: 45–115.5 Gy), assuming α/β = 10. Considering progression at distant sites or death as competing events, the 1- and 2-year actuarial local control rates were 96.5% (95% confidence interval: 84.9–99.7) and 92.6% (95% confidence interval: 79.2–98.7), respectively. According to RECIST, a complete response was achieved in 10 (32.3%) lesions, a partial response in 10 (32.3%) lesions, and stability in 8 (25.8%) lesions. Three patients presented with local relapse at 8.8, 14, and 49.4 months. After a median follow-up of 18 months (range: 4.4–66.4), the median overall survival was 33.5 months (95% confidence interval: 17–not reached), while the median progression-free survival was 7.4 months (95% confidence interval: 3.8–14.1). Treatment-related toxicity was grade 1 or 2 in 42.4% of patients, including nausea (27.3%), abdominal pain (18.2%), vomiting (15.2%), and asthenia (9.1%). None of the patients developed acute grade ≥3 or late toxicity.Conclusion: SBRT seems to be a safe and effective treatment for adrenal gland metastases in patients whose primary tumor and metastatic spread are controlled by systemic treatment. With a 2-year local control rate of 92.6%, SBRT may be considered as one of the first-line treatments in oligometastatic patients with adrenal metastases.