Locoregional Progression-free Survival Research Articles

Randomized Study on Dose Escalation in Definitive Chemoradiation for Patients With Locally Advanced Esophageal Cancer (ARTDECO Study).

To analyze the effect of radiation dose escalation to the primary tumor on local tumor control in definitive chemoradiation (dCRT) for patients with esophageal cancer. Patients with medically inoperable and/or irresectable esophageal carcinoma, referred for dCRT, were randomly assigned between a standard dose (SD) of 50.4 Gy/1.8 Gy for 5.5 weeks to the tumor and regional lymph nodes and a high dose (HD) up to a total dose of 61.6 Gy to the primary tumor. Chemotherapy consisted of courses of concurrent carboplatin (area under the curve 2) and paclitaxel (50 mg/m2) in both arms once a week for 6 weeks. The primary end point was local progression-free survival. Between September 2012 and June 2018, 260 patients were included. Squamous cell carcinoma (SCC) was present in 61% of patients, and 39% had adenocarcinoma (AC). Radiation treatment was completed by 94%, and 85% had at least five courses of chemotherapy. The median follow-up time for all patients was 50 months. The 3-year local progression-free survival (LPFS) was 70% in the SD arm versus 73% in the HD arm (not significant). The LPFS for SCC and AC was 75% versus 79% and 61% versus 61% for SD and HD, respectively (not significant). The 3-year locoregional progression-free survival was 52% and 59% for the SD and HD arms, respectively (P = .08). Overall, grade 4 and 5 common toxicity criteria were 12% and 5% in the SD arm versus 14% and 10% in the HD arm, respectively (P = .15). In dCRT for esophageal cancer, radiation dose escalation up to 61.6 Gy to the primary tumor did not result in a significant increase in local control over 50.4 Gy. The absence of a dose effect was observed in both AC and SCC.

Multimodality Treatment Improves Locoregional Control, Progression-Free and Overall Survival in Patients with Anaplastic Thyroid Cancer: A Retrospective Cohort Study Comparing Oncological Outcomes and Morbidity between Multimodality Treatment and Limited Treatment.

Patients with anaplastic thyroid cancer (ATC) have poor overall survival, and the optimal management approach remains unclear. The aim of this study is to evaluate our experience with multimodality (MMT) versus limited treatment (LT) for ATC. A cohort study of patients with ATC managed in a tertiary referral center was undertaken. The outcomes of MMT were compared with those of LT. The primary outcome measures were locoregional control and progression-free and overall survival. Secondary outcome measures were treatment-related complications and factors associated with improved survival. In total, 59 patients (35 females) with a median age of 73 years (range 39-99 years) and ATC stage IVA (n = 2), IVB (n = 28), or IVC (n = 29) were included. LT was utilized in 25 patients (42%), and 34 cases had MMT. MMT patients had a longer time of locoregional control (18.5 versus 1.9 months; p < 0.001), progression-free survival (3.5 versus 1.2 months; p < 0.001), and overall survival (6.9 versus 2.0 months; p < 0.001) when compared with LT. For patients with stage IVC ATC, locoregional control (p = 0.03), progression-free survival (p < 0.001), and overall survival (p < 0.001) were superior in the MMT cohort compared with LT. MMT had more treatment-related complications than LT (p < 0.001). An Eastern Cooperative Oncology Group performance status < 2 (HR 0.30; p = 0.001) and MMT (HR 0.35; p = 0.008) were associated with improved overall survival. MMT is likely to improve locoregional control, progression-free survival, and overall survival in selected ATC patients including stage IVC tumors but comes with a greater complication risk.

Efficacy of stereotactic body radiotherapy for oligoprogression on PD-1 axis inhibitors in advanced non-small cell lung cancer: A single-center retrospective study.

e21065 Background: Immunotherapy has brought considerable benefit for patients with advanced non-small cell lung cancer (NSCLC), while acquired resistance could occur, of which most were oligoprogression. Adding locoregional therapy into the current systematic treatment could significantly improve the survival of oligoprogressed group. One of the conventional locoregional therapy for oligoprogression is stereotactic body radiotherapy (SBRT), however efficacy of combing SBRT to the ongoing PD-1 axis inhibitors was unclear in oligoprogressive NSCLC. Methods: In this study, we retrospectively reviewed data of patients with advanced NSCLC, who received SBRT on oligoprogressive lesions after acquired resistance to PD-1 axis inhibitor (First line or more) in our hospital, between June 2015 and June 2019. Acquired resistance was defined as initial CR/PR (by RECIST) followed by progression/death. Oligo patterns of acquired resistance were defined as progression in ≤ 3 sites of disease. We summarized the locoregional control rate (LR), progression-free survival (PFS) and overall survival (OS) after SBRT. Results: A total of 18 patients were included, 5 females and 13 males. The median age was 63 years (range: 37-82). 10 (55.6%) patients had a PD-L1 expression &gt; 1%, 13 (72.2%) received combination therapy (anti-PD-1+chemo/antivascular), duration of immunotherapy was longer than 24 months in 9 (50%) patients. After acquired resistance, 25 sites of oligoprogressive lesions were identified (11 in brain, 5 in lung, 3 in lymph node, 3 in bone, 2 in adrenal, 1 in liver), the median maximum dimension was 14.8 cm (range, 10 to 79 cm). The SBRT dose were 30-55 Gy/2-6 fx, with the median biological effective dose at 60 Gy (range: 45-124.8). At a median follow-up of 28.5 months (range: 15-60), 12 (48%) lesions achieved complete response, 7 (28%) had a partial response, 4 (16%) remains stable and 2 (8%) developed progressive disease. The 1 and 2 years’ LR were 100% and 77.8% respectively. The median PFS was 10 months (range: 7-18). Among them, 44.4% and 14.8% had a 1 and 2 years of PFS, and 87.5% and 60% achieved 1-year and 2-year survival respectively. Conclusions: We observed that SBRT for oligoprogression can improve disease control and bring survival benefit, suggesting that SBRT could be considered in patients with oligoprogression after required resistance on immunotherapy in NSCLC. Meanwhile, prospective evaluation or stratified analysis with larger sample size was needed to verify its efficacy and safety in specific group.

The outcomes of cutaneous head and neck angiosarcoma with different treatment modalities and correlation with inflammatory markers.

e23527 Background: Head and neck angiosarcoma (HN-AS) is a distinct entity that commonly arises from the scalp of elderly Asian males. We strive to study the impact of different treatment modalities and explore correlation with blood inflammatory markers. Methods: A prospectively maintained database was queried for patients with biopsy-confirmed HN-AS treated in a single tertiary institution from 2000 to 2018. Results: Eight-eight patients were analyzed. Median age is 73.5 (IQR 66-81.2). Fifty-five (64%) were non-metastatic at diagnosis, seventy-four (84.1%) arose from the scalp and 70.5% were males. Of the 55 non-metastatic patients, 21 received curative surgery and 7 patients received adjuvant radiotherapy. Patients who had curative surgery had smaller tumors (p &lt; 0.001). Local relapses were 57.1% vs 35.7% without and with radiotherapy (p = 0.34). Five patients were still alive at time of analysis but only 1 with a follow up of more than 5 years. In this group, 2-year and 5-year locoregional progression free survival (PFS) were 56.0% and 26.1%, distant PFS were 73.7% and 41.4%, OS were 48.6% and 17.7%. In the group that was metastatic at presentation (n = 31), 17 patients received palliative chemotherapy with 7 patients documented as partial response. 17 patients received palliative radiotherapy with largely good symptomatic relief. Six patients received photodynamic therapy: with 1 documented abscopal response. The median survival is 6.9 months. Overall, 64 patients received palliative chemotherapy and 42 received palliative radiotherapy (in the metastatic or inoperable setting). The most common chemotherapy regimen was single agent paclitaxel (56.3%). In the first line setting, 66.7% experienced at least a partial response to chemotherapy. Comparing the 3 different treatment groups (metastastic vs curative surgery vs non-metastatic/no curative surgery), patient with curative surgery had the best OS (p = 0.007) but worse PFS compared to non-metastatic but no curative surgery patients (p = 0.03). Using full blood count at diagnosis, hazard ratio for neutrophil lymphocyte ratio (NLR) and lymphocyte monocyte ratio (LMR) were 1.02 (p = 0.06) and 0.80 (p = 0.02) respectively for OS. In multivariate analysis, age, stage and LMR were the only 3 significant predictors for OS. Conclusions: Cutaneous HN-AS is an aggressive disease. Although patients who had curative surgery had better overall survival which could be confounded by smaller tumours, and they also had earlier documented relapses possibly due to closer surveillance or tumor growth promotion from post-surgical inflammatory response. The value of adjuvant radiotherapy is unknown. Palliative radiotherapy is useful, and a more hypo-fractionated approach should be favored. Palliative single-agent paclitaxel is effective although overall survival remains grave. Blood inflammatory indicators correlate with survival.

The prognostic impact of daytime and seasonality of radiotherapy on head and neck cancer

BackgroundThe potential impact of daytime and season of radiotherapy application on prognosis is unclear. This was analyzed in a retrospective cohort of patients who were diagnosed with non-metastatic head and neck squamous cell carcinoma (HNSCC) and treated with definitive radiotherapy with or without chemotherapy. Materials and methodsPatient and tumor characteristics, treatment parameters and outcome until last follow-up or death were obtained. Median radiotherapy delivery daytime of each patient was categorized as morning (AM) and afternoon (PM). Treatment season was defined by median date of treatment course. Each year was divided into DARK and LIGHT according to equinoxes. Time-to-event endpoints were defined by first biopsy confirming the HNSCC. ResultsSix hundred fifty-five cases were identified who were treated with (chemo)radiotherapy between 2002 and 2015. Median follow-up was 47 months. No significant heterogeneity in patient, tumor and treatment characteristics were observed between DARK and LIGHT or regarding median daily fraction time (X2 p > 0.05). Five-year loco-regional control (73% vs. 61%; p = 0.0108) and progression-free survival (51% vs. 43%; p = 0.0374) were superior when radiotherapy was administered in DARK. Neither the daytime nor any other treatment time-related parameter affected prognosis. ConclusionThis is the first study investigating and presenting the prognostic impact of seasonality regarding the treatment course on loco-regional control and progression-free survival (DARK > LIGHT). The biological mechanism of action is unclear. These results should be interpreted with caution and our findings have to be validated externally.

Dose-escalated radiotherapy with PET/CT based treatment planning in combination with induction and concurrent chemotherapy in locally advanced (uT3/T4) squamous cell cancer of the esophagus: mature results of a phase I/II trial

BackgroundThis prospective phase I/II trial assessed feasibility and efficacy of dose-escalated definitive chemoradiation after induction chemotherapy in locally advanced esophageal cancer. Primary study endpoint was loco-regional progression-free survival at 1 year.MethodsEligible patients received 2 cycles of induction chemotherapy with irinotecan, folinic acid and 5-fluorouracil weekly and cisplatin every 2 weeks (weeks 1–6, 8–13) followed by concurrent chemoradiation with cisplatin and irinotecan (weeks 14, 15, 17, 18, 20). Radiotherapy dose escalation was performed in three steps (60 Gy, 66 Gy, 72 Gy) using conventional fractionation, planning target volumes were delineated with the aid of 18F-FDG-PET/CT scans. During follow-up, endoscopic examinations were performed at regular intervals.ResultsBetween 09/2006 and 02/2010, 17 patients were enrolled (male/female:13/4, median age: 59 [range 48–66] years, stage uT3N0/T3N1/T4N1: 4/12/1). One patient progressed during induction chemotherapy and underwent surgery. Of 16 patients treated with definitive chemoradiotherapy, 9 (56%) achieved complete response after completion of chemoradiation. One-, 2-, 3- and 5-year overall survival rates (OS) were 77% [95%CI: 59–100], 53% [34–83], 41% [23–73], and 29% [14–61], respectively. Loco-regional progression-free survival at 1, 3, and 5 years was 59% [40–88], 35% [19–67], and 29% [14–61], corresponding cumulative incidences of loco-regional progressions were 18% [4–39%], 35% [14–58%], and 41% [17–64%]. No treatment related deaths occurred. Grade 3 toxicities during induction therapy were: neutropenia (41%), diarrhoea (41%), during combined treatment: neutropenia (62%) and thrombocytopenia (25%).ConclusionsDose-escalated radiotherapy and concurrent cisplatin/irinotecan after cisplatin/irinotecan/5FU induction chemotherapy was tolerable. The hypothesized phase II one-year loco-regional progression free survival rate of 74% was not achieved. Long-term survival compares well with other studies on definitive radiotherapy using irinotecan and cisplatin but is not better than recent trials using conventionally fractionated radiotherapy ad 50 Gy with concurrent paclitaxel or 5FU and platinum compound.Trial registration The present trial was registered as a phase I/II trial at the EudraCT database: Nr. 2005-006097-10 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-006097-10/DE) and authorized to proceed on 2006-09-25.

Outcomes and prognostic factors of major salivary gland tumors treated with proton beam radiation therapy.

Proton beam radiation therapy (PBRT) has dosimetric advantages compared to photon radiation therapy for the treatment of major salivary gland tumors (MSGTs). Patients with non-metastatic MSGTs treated at a single proton therapy center from October 2013 to October 2018 were retrospectively reviewed. Sixty-eight patients with MSGTs were included and the most common site and histology were the parotid gland (75.0%) and adenoid cystic carcinoma (22.1%), respectively. The 3-year rates of locoregional control, progression-free survival, and overall survival were 95.1% (95% CI: 89.9%-100.0%), 80.7% (70.2%-92.7%), and 96.1% (95% CI: 90.9%-100.0%), respectively. In a large cohort of MSGTs treated with PBRT, the rates of locoregional control were high in short-term follow-up and treatment was well tolerated.

Clinical Evidence for Locoregional Surgery of the Primary Tumor in Patients with De Novo Stage IV Breast Cancer

Whether primary tumor surgery is better than no surgery in patients with de novo stage IV breast cancer remains controversial. This study combined prospective clinical trials and a multicenter cohort to evaluate the impact of locoregional surgery in de novo stage IV breast cancer. The GRADE approach was used to assess the quality of evidence in meta-analysis, and propensity score matching analysis was used in the cohort study. This study was registered with PROSPERO CRD42016043766 and ClinicalTrials.gov NCT04456855. A total of 1110 patients from six trials and 353 patients from the cohort study were included. The meta-analysis showed that compared with no surgery, locoregional surgery did not prolong overall survival (hazard ratio [HR]=0.90, P=0.40; moderate-quality) but had a significantly longer locoregional progression-free survival (HR=0.23, P<0.001; moderate-quality). The subgroup analysis of solitary bone-only metastasis (HR=0.47, P=0.04; high-quality) resulted in prolonged overall survival. In the cohort study, locoregional surgery showed a survival benefit (HR=0.63, P=0.041) before matching, but not (HR=0.84, P=0.579) after matching. Patients with bone-only metastasis showed a survival advantage in surgery compared with no surgery before matching (HR=0.36, P=0.034) as well as after matching (HR=0.18, P=0.017). This study indicated that locoregional surgery had a significantly longer locoregional progression-free survival than no surgery in de novo stage IV breast cancer, and patients with bone-only metastasis tended to show an overall survival benefit from surgery.

Concurrent high-dose intensity-modulated radiotherapy and chemotherapy for unresectable locally advanced and metastatic pancreatic cancer: a pilot study

AbstractAim:To evaluate the efficacy of concurrent chemotherapy and high-dose (≥55 Gy) intensity-modulated radiotherapy (CCIMRT) in comparison with chemotherapy alone and intensity-modulated radiotherapy (IMRT) alone for unresectable locally advanced or metastatic pancreatic cancer.Methods:Forty-six patients with pancreatic cancer undergoing CCIMRT (n = 17), chemotherapy alone (n = 16) or IMRT alone (n = 13) were analysed. Overall survival (OS), locoregional progression-free survival (LRPFS) and gastrointestinal toxicities were evaluated. The median radiation dose was 60 Gy (range, 55–60) delivered in a median of 25 fractions (range, 24–30). Gemcitabine (GEM) alone, GEM + S-1, S-1 alone, FOLFIRINOX and GEM + nab-paclitaxel were used in CCIMRT and chemo-monotherapy.Results:The 1-year OS rate was 69% in the CCIMRT group, 27% in the chemotherapy group and 38% in the IMRT group (p = 0·12). The 1-year LRPFS rate was 73, 0 and 40% in the 3 groups, respectively (p = 0·012). Acute Grade ≥ 2 gastrointestinal toxicity (nausea, diarrhea) was observed in 12% (2/17) in the CCIMRT group, 25% (4/16) in the chemotherapy group and 7·7% (1/13) in the IMRT group (p = 0·38). Late Grade 3 gastrointestinal bleeding was observed in 6·3% (1/16) in the chemotherapy group.Conclusion:High-dose CCIMRT yielded acceptable toxicity and favorable OS and LRPFS.

Outcome of chemoradiotherapy using intensity-modulated radiation therapy for cervical esophageal cancer: a single institute experience.

The role of intensity-modulated radiation therapy in the treatment of cervical esophageal cancer remains unclear. The outcome of concurrent chemoradiotherapy for cervical esophageal squamous cell carcinoma using intensity-modulated radiation therapy was retrospectively evaluated. Between 2004 and 2017, 36 patients with cervical esophageal cancer treated with intensity-modulated radiation therapy were included. Among these patients, one had stage II disease, three stage III, 19 stage IVA, and 13 stage IVB. All patients received radiotherapy at a dose of 60Gy and concurrent platinum-based doublet chemotherapy. The median follow-up period for surviving patients was 36months. Three-year locoregional control, progression-free survival, and overall survival rates were 54, 40, and 46%, respectively. Disease progression was noted in 20 out of 36 patients (56%). Grade 3 late toxicities were observed in four patients (three esophageal stenoses and one carotid artery stenosis). There were no grade 4-5 toxicities. Univariate analysis identified the duration of radiotherapy as a prognostic factor for overall survival. Chemoradiotherapy using intensity-modulated radiation therapy for locally advanced cervical esophageal carcinoma achieved satisfactory locoregional control and survival with acceptable toxicities.

Radiotherapy for Primary Tracheal Carcinoma: Experience at a Single Institution

Background:There is limited understanding of tracheal carcinoma (TC) because of its rarity. We examined the efficacy of radiotherapy (RT) for patients with primary TC.Methods:We analyzed the records of 32 patients with primary TC who received RT at our center between November 1996 and December 2016.Results:Thirteen patients received adjuvant RT and 18 received definitive RT. Eight patients achieved complete remission (CR) after definitive RT. Among all patients, the 5-year overall survival (OS) rate was 46.9% and the locoregional progression free survival (LRPFS) rate was 68.1%. Univariate analysis indicated the 5-year OS was better in those with adenoid cystic adenocarcinoma than squamous cell carcinoma (P = 0.001); the 5-year LRPFS was better in patients who received surgical resection than those who did not (92.9% vs 46.4%, P = 0.013) and in patients who received postoperative RT than in those who received definitive RT (91.7% vs 50.1%, P = 0.038). A sub-group univariate analysis indicated the 5-year PFS was better for those who received at least 68 Gy of radiation (44.4% vs 13.0%, P = 0.044). Patients who achieved CR had a better 5-year PFS than those who did not (57.1% vs 10%, P = 0.006). No patients had a toxicity of grade 3 or more.Conclusions:Adjuvant and definitive RT are safe and effective treatments for TC. Patients who received dosages of 68 Gy or more and who had complete tumor regression following definitive RT seemed to have better long-term survival.

Is Locally Advanced Head-Neck Cancer One More Candidate for Accelerated Hypofractionation?

Hypofractionated accelerated radiotherapy (HypoAR) is widely applied for the treatment of early laryngeal cancer. Its role in locally advanced head-neck cancer (LA-HNC) is unexplored. We present results of a prospective trial on 124 patients with LA-HNC, treated with radio-chemotherapy with three different HypoAR fractionations (3.5 Gy/day × 14-15 fractions, 2.7 Gy/day × 20-21 fractions, and 2.5 Gy/day × 21-22 fractions). Protraction of the overall treatment time due to oropharyngeal mucositis was enforced in 18/57 laryngeal, 6/19 nasopharyngeal, and 15/48 cancer patients with other tumors. Regarding late toxicities, laryngeal edema grade 3 was noted in 5/57 patients with laryngeal cancer, while severe dysphagia was noted in 4/124 and tracheoesophageal fistula formation in 1/124 patients. The complete response rates obtained were 73%, 84%, and 67% in patients with laryngeal, nasopharyngeal, and other tumors, respectively. The 3-year locoregional progression-free survival was 58%, 73%, and 55%, respectively. HypoAR chemoradiotherapy is feasible, with acceptable early and late radiotherapy toxicities, response rates and LPFS.

Isotoxic high-dose stereotactic body radiotherapy integrated in a total multimodal neoadjuvant strategy for the treatment of localized pancreatic ductal adenocarcinoma.

Background:Our aim was to evaluate the feasibility and safety of isotoxic high-dose (iHD) stereotactic body radiation therapy (SBRT) in a total neoadjuvant sequence for the treatment of localized pancreatic adenocarcinoma.Materials and methods:Biopsy-proven borderline resectable/locally advanced pancreatic cancer (BR/LAPC) patients were included in this observational prospective analysis from August 2017 to April 2020 without excluding tumours showing a radiological direct gastrointestinal (GI) invasion. An induction chemotherapy by modified fluorouracil, irinotecan and oxaliplatin was performed for a median of six cycles. In case of non-progression, an isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT) was delivered in 5 fractions followed by a surgical exploration. The primary endpoint was acute/late gastrointestinal grade ⩾3 toxicity. Secondary endpoints were overall survival (OS), progression-free survival (PFS) and local control (LC).Results:A total of 39 consecutive patients (21 BR and 18 LAPC) were included: 34 patients (87.2%, 18 BR and 16 LAPC) completed the planned neoadjuvant sequence. After iHD-SBRT, 19 patients [55.9% overall, 13/18 BR (72.2%) and 6/16 LAPC (37.5%)] underwent an oncological resection among the 25 patients surgically explored (73.5%). The median follow up was 18.2 months. The rates of acute and late GI grade 3 toxicity were, respectively, 2.9% and 4.2%. The median OS and PFS from diagnosis were, respectively, 24.5 and 15.6 months. The resected patients had improved median OS and PFS in comparison with the non-resected patients (OS: 32.3 versus 18.2 months, p = 0.02; PFS: 24.1 versus 7.1 months, p < 0.001). There was no survival difference between the BR and LAPC patients. The 1-year LC from SBRT was 74.1% and the median locoregional PFS was not reached for both BR and LAPC patients.Conclusions:iHD-SBRT displays an excellent toxicity profile, also for potentially high-risk patients with radiological direct GI invasion at diagnosis and can be easily integrated in a total neoadjuvant strategy. The oncological outcomes are promising and emphasise the need for further exploration of iHD-SBRT in phase II/III trials.

Hypofractionated intensity-modulated radiotherapy with concurrent chemotherapy for elderly patients with locally advanced pancreatic carcinoma

BackgroundIt is important to understand how elderly patients with locally advanced pancreatic carcinoma (LAPC) should be treated, since the number of elderly cancer patients will increase. However, the optimal treatment for elderly patients with LAPC remains unclear. The purpose of this study was to evaluate the efficacy and safety of hypofractionated intensity-modulated radiotherapy (IMRT) with concurrent gemcitabine for elderly patients with LAPC.MethodsWe retrospectively analysed the data from LAPC patients aged ≥ 75 years treated with hypofractionated IMRT (48 Gy in 15 fractions) with concurrent weekly gemcitabine at our institution from February 2013 to December 2018. Overall survival (OS), progression-free survival (PFS), locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), and the pattern of recurrence and toxicity were analysed.ResultsFifteen patients received treatment during the study period. The median age was 78 years (range 75–86 years), and the Eastern Cooperative Oncology Group (ECOG) performance status (PS) of all patients was 0–1. The median survival time (MST) and median PFS were 20.4 [95% confidence interval (CI) 10.3–36.8] and 13.5 (95% CI 6.4–20.3) months, respectively, and the 1-year OS and PFS rates were 80.0% (95% CI 50–93.1%) and 66.7% (95% CI 37.5–84.6%), respectively. The median LRPFS and median DMFS were 15.6 (95% CI 6.4–36.8) and 14.9 (95% CI 7.0–20.5) months, respectively, and the 1-year LRPFS and DMFS rates were 73.3% (95% CI 43.6–89.1%) and 66.7% (95% CI 37.5–84.6%), respectively. Non-haematologic grade 3 toxicity was observed in three cases, of which only one was induced by radiotherapy, whereas grade 4–5 non-haematologic acute or late toxicities were not observed.ConclusionsThe OS and PFS of elderly patients with LAPC treated using hypofractionated IMRT with concurrent gemcitabine were favourable and without the occurrence of severe toxicity. This treatment strategy is feasible and promising for elderly LAPC patients with good PS.

Boron neutron capture therapy using cyclotron-based epithermal neutron source and borofalan (10B) for recurrent or locally advanced head and neck cancer (JHN002): An open-label phase II trial

Background and purposeBoron neutron capture therapy (BNCT) can be performed without reactors due to development of cyclotron-based epithermal neutron source (C-BENS), which is optimized for treatment for deeper-seated tumors. The purpose of this study was to evaluate efficacy and safety of cyclotron-based BNCT with borofalan (10B) for recurrent or locally advanced head and neck cancer. Materials and methodsIn this open-label, phase II JHN002 trial of BNCT using C-BENS with borofalan (10B), patients with recurrent squamous cell carcinoma (R-SCC) or with recurrent/locally advanced non-squamous cell carcinoma (R/LA-nSCC) of the head and neck were intravenously administered 400 mg/kg borofalan (10B), followed by neutron irradiation. The tumor dose was determined passively as the mucosal maximum dose of 12 Gy-Eq. The primary endpoint was the objective response rate (ORR). Post-trial observational JHN002 Look Up study was planned for evaluating locoregional progression-free survival (LRPFS). ResultsEight R-SCC and 13 R/LA-nSCC patients were enrolled. All R-SCC patients had prior radiotherapy with a median dose of 65.5 Gy (range, 59.4–76.0 Gy). The ORR for all patients was 71%, and complete response/partial response were 50%/25% in R-SCC and 8%/62% in R/LA-nSCC. The 2-year overall survival for R-SCC and R/LA-nSCC were 58% and 100%, respectively. The median LRPFS was 11.5 months for R-SCC. Frequently observed adverse events included alopecia (95%), hyperamylasemia (86%), and nausea (81%). ConclusionThese data suggest that BNCT using C-BENS with borofalan (10B) is a promising treatment option for patients with R-SCC or R/LA-nSCC of the head and neck.

288P Application of volumetric modulated arc therapy (VMAT) in head and neck cancers: 5-year single institutional experience

Head and neck carcinomas are still a common cancer in Vietnam, where radiotherapy plays a vital role in both curative and palliative treatments. Volumetric Modulated Arc Therapy was developed since first decade of 21st century in the developed countries such as the United States of America, Japan, etc. In Vietnam, Vinmec Times City International Hospital has applied this technique in treating cancer patients since December 2014. Retrospective study of 22 non-metastatic head and neck cancer patients from December 2014 to January 2020 at Vinmec Times City International hospital, Hanoi, Vietnam, were evaluated. Twenty two (ages 26-75 years-old; average age: 54.14±11.41, male-female ratio: 14/8) non-distant metastatic head and neck cancer patients, [14 nasopharyngeal carcinomas (NPC), 2 oropharyngeal carcinomas (OPC), 6 laryngo-hypopharyngeal carcinomas (HPC), stage II- 8 patients (36.4%); stage III 7 patients (31.8%) and stage IV 7 patients (31.8%)] were curatively treated with simultaneous integrated boost- volumetric modulated arc therapy (SIB-VMAT) in combination with chemotherapy, given fractionation was 70Gy (2Gy/fraction for 35 fractions as standard fractionation) for high-risk planning target volume (PTV7000), 63Gy for intermediate-risk PTV (PTV6300) and 56Gy for low-risk PTV (PTV5600). There were 11 undifferentiated carcinomas of nasopharynx, the remainder were squamous cell carcinomas. Regarding response rate, complete response was seen in 14 patients (63.6%), partial response seen in 8 patients (36.4%). Survival analysis showed that mean survival was 52.2 ±4.4 (months) (CI 0.95; 43.5-60.9); overall survival (OS), 1 year OS, 2 year OS, 3 year OS was 86.4%; 100%; 100% and 85.7%, respectively. Loco-regional progression-free survival (LRFS), 1 year, 2 year and 3 year LRFS was 81.8%; and 95.5%; 82.7%; 82.7% respectively. The acute toxicities were skin reaction [7 patients (31.9%) with grade 1, 12 patient (54.5%) with grade 2, 3 patients (13.6%) with grade 3], stomatitis [8 patients (36.4%) grade 1; 12 patients (54.5%) grade 2; 2 patients (9.1%) grade 3]. Late toxicities seen were radiation-related sclerosis dermatitis [only 3 patients (13.6%) grade 1]; stomatitis seen in only 6 patients (27.3%) grade 1; dry mouth, only grade 1 in 14 patients (63.6%); dysphagia 6 patients (27.3%) grade 1. SIB-VMAT for head and neck cancers was safely and effectively applied in our institution with the good outcomes and very few toxicities.

Sequential Hypofractionated Radiotherapy can Offer Similar Disease Control and Survival of Concurrent Chemoradiation for Stage III Non-Small Cell Lung Cancer?

Concurrent conventional fractionated chemoradiation (ccCRT) is the standard of care for locally advanced non-small cell lung cancer (LA-NSCLC) when compared with convectional fractionated radiation therapy (cfRT) after chemotherapy. The main benefit of ccCRT is associated to disease locoregional control. Sequential Hypofractionated Radiation therapy (s-HypoRT) is a treatment option for these patients. We compared the outcomes of the ccCRT with sequential treatment cfRT and s-HypoRT. It was a retrospective analysis of all inoperable stage III LA-NSCLC submitted to radical radiotherapy (RT) in a single institution from January 2013 to October 2018. Patients submitted to ccCRT and cfRT received 60Gy in 30 fractions. The patients submitted to s-HypoRt received 55Gy in 20 fractions. All patients were treated with conformal RT or IMRT. All chemotherapy schedule was platinum doublet based. Patients submitted All Patients were (re)staged according to the AJCC 8a ed. The criteria for disease progression was based on RECIST v1.1 and the toxicity criteria used was the CTCAE.v4. Survival analysis was evaluated by Kaplan–Meier method and log-rank test. Multivariate models were tested including all covariates with p values < .20 in the univariate analysis. It was recorded the medical charts and treatment planning of 140 patients. The median age was 63 years (range, 25–83). Most were male (61%) and had ECOG Performance Status 1 (72%). The stage distribution was IIIA 32%, IIIB 51% and IIIC 17%. The patient populations were divided in 3 groups: 52 patients (37%) were submitted to cc-CRT, 38 patients (27%) was submitted to sequential cfRT (cfRTSeq) and 50 patients (36%) received s-HypoRT. With the median follow up of 16 months, the median Overall Survival (OS) for the entire population was 23 months and there was no difference in OS between the 3 groups (p = 0,686). Large tumor volume (p = 0,039) and use of IMRT (p = 0,031), was associated with OS on univariate analysis. The 2-years Locoregional Progression Free Survival (LPFS) 62.9% for ccCRT, x 60.0% for s-HypoRT and 41.0% for cfRTSeq (p = 0.031). On multivariate analysis the cfRTSeq (HR 2,11, IC 1,06—4,19) was associated with worse LRPFS. The treatment was well tolerated for all groups, and the rates of grade ≥ 3 acute esophagitis of 1.9% for ccCRT and 4.0% for s-HypoRT (p = ns). Only one case of grade 3 fatigue was evidenced in the cfRTSeq and one case of grade 3 pneumonitis was evidenced in the ccCRT and cfRT group. Our data demonstrated that s-HypoRT results in similar LRPFS when compared with the standard ccCRT. There was no difference in OS. S-HypoRT is a safe and fast treatment strategy for patients not suitable for ccCRT and can be considered a better option than cfRTSeq.

Adjuvant Radiation Therapy for Pleural Mesothelioma after Extrapleural Pneumonectomy (EPP) or Pleurectomy and Decortication (P+D)

The optimal treatment sequence for localized malignant pleural mesothelioma (MPM) is controversial. We hypothesized that pleurectomy and decortication (P+D) followed by adjuvant intensity modulated radiation therapy (IMRT) has equivalent cancer control with less morbidity than extrapleural pneumonectomy (EPP) followed by adjuvant radiation therapy (RT). Forty-four patients treated with curative intent surgery and adjuvant RT for MPM at a single institution were included. Prior to September 2013, patients were treated with EPP followed by adjuvant RT (n = 24, 54%). After September 2013, standard treatment was P+D followed by adjuvant IMRT (n = 20, 45%). We compared oncologic outcomes and toxicities (CTCAE version 5.0) between these two approaches. Median age at diagnosis was 64 years (range 26-76); patients receiving EPP were significantly younger (median age 60 vs. 70, p<0.01). Most patients were AJCC 8th edition clinical stage T1 (80%) and N0 (91%). Thirty-seven patients (84%) received neoadjuvant chemotherapy. At surgery, pathologic T stage was most commonly T3 (64%), with 30% node positive. Forty-two patients (95%) had epithelioid histology at surgery, and the remaining two had biphasic histology (5%). Median total RT dose to the entire pleura was 45 Gy (range 30-60 Gy), delivered over a median 27 fractions (range 20-33). Median follow-up for the entire cohort was 3.9 years (range 0.6-20.0 years). Median OS was 2.6 years for P+D compared to 1.1 years for EPP (HR: 0.52, 95% CI: 0.25-1.09, p = .08). Two-year OS was 63% for P+D versus 21% for EPP. On univariate analysis, male sex, pre-operative FEV1% <80, and clinically positive nodes were significantly associated with risk of death. There was no difference in locoregional control (LRC) or progression-free survival (PFS) between P+D and EPP. LRC at 2 and 5 years for the entire cohort was 48% and 39%. PFS at 2 and 5 years was 34% and 17%. Acute Grade 2+ pneumonitis was seen in 0% of EPP patients compared to 35% for P+D, with one grade 3 (5%), one grade 4 (5%), and no grade 5 (0%) pneumonitis. Mean lung dose was significantly associated with development of any grade pneumonitis (odds ratio: 1.46, 95% CI: 1.02-2.11, p = 0.04). Patients who developed pneumonitis had a mean total lung mean dose of 20.4 Gy, compared to 12.9 Gy in those who did not. Total lung V20% was also significantly associated with development of any grade pneumonitis (odds ratio: 1.11, 95% CI: 1.01-1.22, p = 0.03). Mean total lung V20% was 38% for those who developed pneumonitis, compared to 20% for those who did not. FEV1% declined by 27% after P+D and 32% after EPP, while DLCO% declined by 22% after P+D and 28% after EPP. Modern treatment with pleurectomy and decortication followed by adjuvant hemithoracic IMRT appears to provide favorable survival compared to EPP followed by RT, though more non-fatal pneumonitis was seen after P+D with adjuvant IMRT.

Correlative Analyses Between Immune Markers, Tumor Hypoxia And Outcomes Of Head-And-Neck Cancer Patients Undergoing Chemoradiation: Results From A Prospective Trial

Tumor-infiltrating lymphocytes (TILs) influence the response of patients with head-and-neck squamous cell carcinomas (HNSCCs) to chemoradiation and are modulated by the tumor microenvironment and tumor-associated hypoxia. This analysis aimed to assess the prognostic value of TILs and their association with the dynamic tumor hypoxia during chemoradiation in a prospective trial of HNSCC patients. 49 patients with locally advanced HNSCCs were enrolled in this prospective trial prior to undergoing definitive chemoradiation. Patients received tumor biopsies and [18F]-FDG-PET imaging at baseline and [18F]-FMISO hypoxia PET at baseline and in weeks 2 and 5 into treatment. Total lymphocytes, CD3-, CD4-, CD8-positive lymphocytes and expression of PD-1 and PD-L1 were quantified by immunohistochemistry in tumoral and stromal areas of the biopsies and correlated with the tissue hypoxia markers HIF1α, CAIX, CD34 and the longitudinal hypoxia PET/CT data. Potential correlations of immune markers with locoregional control and patient survival were assessed. Patients with high TIL numbers demonstrated increased locoregional control (p = 0.007) and progression-free survival (p = 0.003) compared to patients with lower levels in the biopsies. High numbers of CD3-positive T lymphocytes correlated with improved progression-free (p = 0.018) and overall survival (p = 0.037). In contrast, there was a trend towards impaired progression-free survival for high numbers of CD4-positive regulatory T lymphocytes (p = 0.091), while neither CD8-positive cytotoxic T lymphocytes nor PD-1 or PD-L1 expression correlated with patient outcomes. High levels of TILs were linked to an increased density of CD34-positive microvessels, but not increased levels of hypoxia markers HIF1α or CAIX. No significant correlations could be observed between TILs and dynamic hypoxia PET imaging parameters. In contrast, high expression of intratumoral and stromal PD-1 was associated with low initial tumor hypoxia levels (p = 0.023 for intratumoral PD-1, p = 0.004 for stromal PD-1) as well as a further decrease in the PET hypoxia signal between treatment initiation and week 5 (p = 0.033 for intratumoral PD-1, p = 0.001 for stromal PD-1). In this trial, infiltration of CD3-positive, but not CD4-positive or CD8-positive lymphocytes correlated with an improved locoregional control and increased survival of HNSCC patients after chemoradiation. While no clear associations were found between lymphocyte counts and tumor hypoxia, tumoral PD-1 expression was linked to low initial hypoxia levels and further reductions during treatment. The interplay between tumor hypoxia and tumor-associated immune patterns warrants further investigations to predict treatment response of HNSCC patients.

Definitive Intent Locoregional IMRT In Oligometastatic Anal Squamous Cell Carcinoma

The role of locoregional intensity modulated radiation therapy (IMRT) in patients with metastatic anal squamous cell carcinoma (SCC) remains undefined. There is growing evidence of the potential benefit of local therapy even in the setting of oligometastatic disease to prevent the morbidity of uncontrolled pelvic disease. We queried an institutional database of 358 consecutive patients with SCC of the anal canal treated with definitive intent pelvic IMRT from 2005 to 2018 to identify patients with de novo metastatic disease. Locoregional control (LRC), progression-free survival (PFS), and overall survival (OS) were computed using the Kaplan-Meier method. Acute and late toxicities were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Twenty-five patients with a median follow-up of 26 months including 19 (76%) women and 6 (24%) men with a median age of 60 years comprised the evaluable cohort. Eight (32%) patients had a solitary metastasis, 10 (40%) had two metastatic lesions, 2 (8%) had three metastatic lesions, 5 (20%) had four or more metastatic lesions. Non-regional lymph nodes were the most common site of metastatic disease (N = 16, 49%) followed by liver (N = 10, 30%), lung (N = 4, 12%), and others (N = 3, 9%). Sixteen patients had HPV related disease and 3 patients were HIV+. The median dose to the primary tumor was 56Gy (range, 50-58Gy) in a median of 28 fractions (range, 25-29) over a median of 39 elapsed days (range, 35-55). Twelve (48%) patients received induction chemotherapy and all patients received concurrent chemotherapy predominately mitomycin and capecitabine based. Twenty-one (84%) patients had metastatic-directed ablative therapy which included radiation (N = 20, 80%) and IR-ablation (N = 1, 4%). No patients underwent metastasectomy or received additional chemotherapy, targeted therapy, or immunotherapy prior to progression of disease. The 3-year LRC was 81%, PFS was 27%, and OS was 53%. In comparing patients with non-regional lymph node involvement to patients with visceral organ involvement there was no significant difference in LRC (86% vs. 79%, p = 0.950) but a trend for improved PFS (71% vs. 18%, p = 0.069) and OS (86% vs. 49%, p = 0.365). Grade 3+ acute toxicity included dermatitis (12%), proctitis (4%), and diarrhea (4%). Late grade 2+ toxicity rate was 12%. Definitive intent pelvic IMRT provides excellent locoregional control in patients with oligometastatic anal SCC. Local and extended regional nodal radiation is important to prevent the significant morbidity of uncontrollable pelvic disease given durable PFS and OS in patients with oligometastatic anal SCC.