Involved-field Radiotherapy Research Articles

Adjuvant rituximab and elevated intratumoural CD8 expression are associated with sustained disease control after radiotherapy in a randomised trial of systemic therapy in early-stage follicular lymphoma

We report extended follow-up of TROG99.03, a randomised phase III trial in early-stage follicular lymphoma (ESFL) including new information on the role of adjuvant rituximab and translational studies. Patients with ESFL were randomised to involved field radiotherapy (IFRT) or IFRT plus 6-cycles cyclophosphamide/vincristine/prednisolone (IFRT+CVP). From 2006 rituximab was added to IFRT+CVP (IFRT+R-CVP). Clinical and multi-omic parameters were evaluated. Findings were validated in two independent ESFL cohorts (99 and 60 patients respectively). Between 2000 and 2012, 150 (75 per arm) patients were recruited. 48% were positron emission tomography (PET)-staged. By protocol, at median follow-up 11.3-years, progression-free survival (PFS) remained superior for IFRT+(R)CVP vs. IFRT (hazard ratio [HR]=0.60, 95% CI=0.37-0.98, p=0.043; 10-year PFS 62% vs. 43%) respectively. Although no significant difference in overall survival was observed (HR=0.44, 95% CI=0.16-1.18, p=0.11, 10-year OS 95% vs. 84%), patients receiving IFRT+(R)CVP experienced fewer composite (histological transformation and death) events (p=0.045). PFS of IFRT+R-CVP-treated patients compared with all other treatments lacking rituximab (IFRT alone plus IFRT+CVP) was superior (HR=0.36, 95% CI=0.13-0.82, p=0.013). Amongst PET-staged patients, PFS differences between IFRT+R-CVP vs. IFRT were maintained (HR=0.38, 95% CI=0.16-0.89, p=0.027) indicating benefit distinct from stage migration. FL-related mutations and BCL2-translocations were not associated with PFS. However, by multivariate analysis elevated CD8A gene expression in diagnostic biopsy tissue was independently associated with improved PFS (HR=0.45, 95% CI=0.26-0.79, p=0.037), a finding confirmed in both ESFL validation cohorts. CD8A gene expression was raised (p=0.02) and CD8+ T-cell density higher within follicles in ESFL vs. advanced-stage FL (p=0.047). Human leucocyte antigen class I specific neoantigens were detected in 43% of patients, suggesting neoantigen-specific CD8+ T-cells have a role in confining the spread of the disease. Adjuvant R-CVP and elevated intratumoural CD8 expression were independently associated with sustained disease control after radiotherapy in ESFL. Cancer Council Victora; National Health and Medical Research Council; Leukaemia Foundation; Mater Foundation.

Could elective nodal irradiation for locally advanced rectal cancer be omitted in the context of total neoadjuvant therapy? An analysis of the recurrence sites of rectal cancer

PurposeThis study aims to optimize neoadjuvant radiotherapy target area for locally advanced rectal cancer (LARC) patients undergoing total neoadjuvant therapy (TNT) by examining local recurrence patterns.Methods and materialsWe retrospectively analyzed the clinical data of rectal cancer patients who undergone local recurrence after surgery. Recurrence sites were categorized and compared with initial diagnosis imaging, focusing on visible and suspicious lesions.ResultsOf the 126 patients who met our criteria, 186 lesions were analyzed. Within these, 75.40% of cases (95/126) and 83.33% of lesions (155/186) were located within the pelvic cavity. Conversely, 3.97% of cases (5/126) and 3.33% of lesions (6/186) occurred outside the pelvic cavity. Additionally, 20.63% of cases (26/126) and 13.44% of lesions (25/186) were found in both regions. Recurrences were predominantly observed in mesenteric regions (MR) (40.86%, 76/186) and presacral regions (PR) (32.26%, 60/186). In addition, 86.51% of patients (109/126) had recurrent lesions in HRA and the suspected lesions areas. Further analysis showed that initial CEA levels and adjuvant therapy types were identified as independent predictors for recurrence in MR/PR and initially suspected lesions. 86.51% of patients had recurrent lesions in HRA and the suspected lesions areasConclusionThe MR, PR, and areas of initial suspicious lesions are high-risk zones for post-surgical recurrence of LARC. Exploratory study of involved-field irradiation (IFI) can be carried out in the context of TNT in LARC.

Radiotherapy with S-1 for the treatment of esophageal squamous cell carcinoma 75 years or older

ObjectiveExplore the efficacy and safety of involved-field irradiation (IFI) combined with S-1 as definitive concurrent chemoradiotherapy (dCRT) for locally advanced elderly esophageal squamous cell carcinoma (ESCC), under the premise of intensity-modulated radiotherapy (IMRT).MethodsWe designed a prospective single-arm phase II study. The study enrolled 91 patients aged 75 to 92 years. Eligible participants had histologically confirmed squamous cell carcinoma, stage II to IV disease based on the 8th edition of the American Joint Committee on Cancer (AJCC). All elderly patients (EPs) received dCRT with S-1. which was administered orally twice daily for 28 days. The radiotherapy dose was 61.2 Gy delivered in 34 fractions or 50.4 Gy delivered in 28 fractions. The primary endpoint was 2-year overall survival (OS), and the secondary endpoints were progression-free survival (PFS), local control rate (LCR), and safety.ResultsFrom July 2017 to July 2021, we enrolled EPs with ESCC who were treated at the Jiangsu Cancer hospital. As of August 1, 2023, the median follow-up of surviving EPs was 31.4 months (IQR: 25.2 to 72.6 months). 83 patients (91.2%) completed the whole course of treatment. The 2-year OS rate was 59.2%, and the PFS rate was 43.7%. The most common grade 1 to 2 adverse effects (AEs) were radiation esophagitis (79.1%), and then were radiation pneumonia (46.2%). Anemia (41.8%) was the most common of grade 1 to 2 hematologic toxicity. The incidence of grade 3 or above AEs was 24.2%, and the incidence of leukopenia was the highest (11.0%). There was not one death due to treatment-related toxicity. In a subgroup analysis of radiotherapy doses, we found no statistically significant differences in PFS (P = 0.465) and OS (P = 0.345) in EPs with ESCC who received 50.4 Gy and 61.2 Gy, and that patients in the 50.4 Gy group had lower dermatitis (P = 0.045) and anemia (P = 0.004).ConclusionsIF-IMRT combined with S-1 is a promising regimen for elderly ESCC. And the radiotherapy dose of 50.4 Gy remains the standard dose for EPs with ESCC undergoing CCRT.

Adebrelimab plus chemotherapy and sequential thoracic radiotherapy as first-line therapy for extensive-stage small–cell lung cancer (ES-SCLC): a phase II trial

This phase II prospective trial aimed to investigate the efficacy and safety of adebrelimab (PD-L1 antibody) plus first-line chemotherapy followed by sequential thoracic radiotherapy (TRT) combined with adebrelimab in extensive-stage small-cell lung cancer (ES-SCLC). Biomarkers associated with potential therapeutic effects were also explored. Patients with previously untreated ES-SCLC were enrolled at Shandong Cancer Hospital and Institute (Jinan, China). Patients received 4-6 cycles of adebrelimab (20mg/kg, D1, Q3W) combined with EP/EC (etoposide, 100mg/m2, D1-3, Q3W and cisplatin, 75mg/m2, D1, Q3W or carboplatin, AUC=5, D1, Q3W). Then patients with response sequentially underwent consolidative TRT (≥30Gy in 10 fractions or≥50Gy in 25 fractions, involved-field irradiation), and maintenance adebrelimab until disease progression or intolerable adverse events (AEs). The primary endpoint was overall survival (OS). Genomic and circulating tumour DNA (ctDNA) profiling were also analyzed with tumour tissues and peripheral blood. This trial was registered with ClinicalTrials.gov, NCT04562337. From October 2020 to April 2023, 67 patients diagnosed with ES-SCLC were enrolled and received at least one dose of study treatment. All patients were included in the efficacy and safety analyses. 45 patients received sequential TRT as planned. The median OS and progression-free survival (PFS) was 21.4 months (95% CI: 17.2-not reached months) and 10.1 months (95% CI: 6.9-15.5 months), respectively. The confirmed objective response rate was 71.6% (48/67, 95% CI: 59.3-82.0%) and disease control rate was 89.6% (60/67, 95% CI: 79.7-95.7%). There were no treatment-related deaths. The most common grade 3 or higher treatment-related adverse events (TRAEs) were hematological toxicities. The incidence of any grade and G3+ pneumonitis was 25% (17/67) and 6% (4/67), respectively. No unexpected adverse events were observed. Patients without co-mutations of TP53/RB1 in both tissue and peripheral blood displayed longer PFS (tissue, P=0.071; ctDNA, P=0.060) and OS (tissue, P=0.032; ctDNA, P=0.031). Adebrelimab plus chemotherapy and sequential TRT as first-line therapy for ES-SCLC showed promising efficacy and acceptable safety. This study was funded by the National Natural Science Foundation of China (82172865), Jiangsu Hengrui Pharmaceuticals Co., Ltd. and Amoy Diagnostics Co., Ltd.

Concurrent chemoradiotherapyof different radiation doses and different irradiation fields for locally advanced thoracic esophageal squamous cell carcinoma: A randomized, multicenter, phase III clinical trial.

Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal radiotherapy regimen, particularly in terms of total dose and planned range of irradiation field, remains unclear. This phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target fields. This trial compared two aspects of radiation treatment, total dose and field, using a two-by-two factorial design. The high-dose (HD) group received 59.4Gy radiation, and the standard-dose (SD) group received 50.4 Gy. The involved field irradiation (IFI) group and elective nodal irradiation (ENI) group adopted different irradiation ranges. The participants were assigned to one of the four groups (HD+ENI, HD+IFI, SD+ENI and SD+IFI). The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS). The synergy indexwas used to measure the interaction effect between dose and field. The interaction analysis did not reveal significant synergistic effects between the dose and irradiation field. In comparison to the target field, patients in IFI or ENI showed similar OS (hazard ratio [HR] = 0.99, 95% CI: 0.80-1.23, p = 0.930) and PFS (HR = 1.02, 95% CI: 0.82-1.25). The HD treatment did not show significantly prolonged OS compared with SD (HR = 0.90, 95% CI: 0.72-1.11, p = 0.318), but it suggested improved PFS (25.2 months to 18.0 months). Among the four groups, the HD+IFI group presented the best survival, while the SD+IFI group had the worst prognosis. No significant difference in the occurrence of severe adverse events was found in dose or field comparisons. IFI demonstrated similar treatment efficacy to ENI in CCRT of ESCC. The HD demonstrated improved PFS, but did not significantly improve OS. The dose escalation based on IFI (HD+IFI) showed better therapeutic efficacy than the current recommendation (SD+ENI) and is worth further validation.

Local radiotherapy and measurable residual disease-driven immunotherapy in patients with early-stage follicular lymphoma (FIL MIRO): final results of a prospective, multicentre, phase 2 trial

The mainstay of treatment for early-stage follicular lymphoma is local radiotherapy, with a possible role for anti-CD20 monoclonal antibody (mAb). We aimed to evaluate the effect of these treatments using a measurable residual disease (MRD)-driven approach. This prospective, multicentre, phase 2 trial was conducted at 27 centres of the Fondazione Italiana Linfomi (FIL) in Italy. Eligible participants were adults (≥18 years) with newly diagnosed, histologically confirmed follicular lymphoma (stage I or II; grade I-IIIa). Patients were initially treated with 24 Gy involved-field radiotherapy over 12 days; those who were MRD-positive after radiotherapy or during follow-up received eight intravenous doses (1000 mg per dose; one dose per week) of the anti-CD20 mAb ofatumumab. The primary endpoint was the proportion of patients who were MRD-positive after involved-field radiotherapy and became MRD-negative after ofatumumab treatment. Patients were included in the primary endpoint analysis population if they were positive for BCL2::IGH rearrangement at enrolment in peripheral blood or bone marrow samples. MRD positivity was defined as the persistence of BCL2::IGH rearrangement in peripheral blood or bone marrow, assessed centrally by laboratories of the FIL MRD Network. The trial was registered with EudraCT, 2012-001676-11. Between May 2, 2015, and June 1, 2018, we enrolled 110 participants, of whom 106 (96%) were eligible and received involved-field radiotherapy. Of these, 105 (99%) were White, one (1%) was Black, 50 (47%) were male, and 56 (53%) were female. Of 105 participants in whom BCL2::IGH status was evaluable, 32 (30%) had a detectable BCL2::IGH rearrangement at baseline. After radiotherapy, 12 (40%) of 30 patients reached MRD-negative status, which was long-lasting (at least 36 or 42 months) in three (25%). In those who were MRD-positive after radiotherapy, ofatumumab induced MRD-negativity in 23 (92%; 95% CI 74-99) of 25 evaluable patients. After a median follow-up of 46·1 months (IQR 42·8-50·8), 14 (61%) of these 23 patients remain in complete response and are MRD-negative. The most common grade 3-4 adverse events were infusion-related reactions, observed in four patients. Local radiotherapy is frequently not associated with the eradication of follicular lymphoma. An MRD-driven, anti-CD20 monoclonal antibody consolidation enables molecular remission to be reached in almost all patients and is associated with a reduced incidence of relapse over time. A clinical advantage of an MRD-driven consolidation is therefore suggested. AIRC Foundation for Cancer Research in Italy, Novartis International, and GlaxoSmithKline.

P-GEMOX with sequential or sandwiched radiotherapy for early-stage extranodal natural killer/T-cell lymphoma.

7075 Background: Combined modality therapy (CMT), namely chemotherapy combined with radiotherapy, has been recommended for patients with localized extranodal natural killer/T-cell lymphoma (ENKTL). However, the optimal CMT has not been fully clarified. As chemotherapy is more easily accessible than immediate radiotherapy in the routine clinical practice, the “chemotherapy-first” CMT including sequential or sandwiched radiotherapy deserves further exploration. In addition, the optimal non-anthracycline-based regimen needs to be confirmed. Methods: The P-GEMOX regimen was administrated as follows: pegaspargase 2000 IU/m2 intramuscular on day 1, gemcitabine 1000 mg/m2 intravenous on day 1 and 8, oxaliplatin 130 mg/m2 intravenous on day 1 and was repeated every 21 days. Patients who achieved at least stable disease (SD) subsequently underwent involved field radiotherapy (IFRT). The dose of IFRT ranged from 50 to 55 Gy. Performing sequential radiotherapy (4 cycles of CT+RT) or sandwich radiotherapy (2 cycles of CT+RT+2 cycles of CT) is determined by the clinician based on the patients' conditions. The primary endpoint was the overall response rate (ORR) after 2 cycles of chemotherapy, and secondary study endpoints were CR, PFS, and OS. Safety was also evaluated. Results: From August 2020 to April 2023, thirty-seven patients (23 men, 14 women; median age: 55, 26-76 years) with stage I/II ENKTL who had received P-GEMOX were collected. 14 patients were stage IE and 23 were IIE. ALL patients completed at least 2 cycles of P-GEMOX, which resulted in 94.6% (35/37) of ORR including 30 patients with CR and 5 patients with PR. Among the patients in remission, 15 patients received sequential radiotherapy, 15 received sandwich radiotherapy, 4 were waiting for or in the process of radiotherapy, and 1 patient progressed before radiotherapy. With a median follow-up of 14.8 months (range: 2.6-38.1 months), the 3-year PFS and OS were 87.2% (95%CI 69.3%-95%) and 90.6% (95%CI 72%-97.1%), respectively. Sandwich radiotherapy had an obvious trend for longer PFS than sequential radiotherapy (18moths-PFS 100% vs. 78%; P=0.073). During the treatment, 21.6% (8/37) of the patients experienced grade 3–4 treatment-emergent adverse events (TEAEs). The most grade 3–4 hematological TEAEs were neutropenia (7/37, 18.9%) and thrombocytopenia (4/37, 10.8%). As for grade 3–4 non-hematological TEAEs, elevated aminotransferase, hyperbilirubinemia and hypofibrinogenemia were 16.2%, 10.8% and 8.1%, respectively. The adverse events of this CMT were well-tolerated and manageable. No treatment-related death occurred. Conclusions: Our study demonstrated that CMT consisted of P-GEMOX showed favorable efficacy with acceptable toxicity, and sandwich radiotherapy (CT+RT+CT) seems give more favorable PFS than sequential radiotherapy. The CMT protocol could be an effective treatment option for early-stage ENKTL patients.

Overall survival of adebrelimab plus chemotherapy and sequential thoracic radiotherapy as first-line treatment for extensive-stage small cell lung cancer.

8014 Background: The phase 3 trial (CAPSTONE-1) showed that adebrelimab (PD-L1 antibody) combined with first-line chemotherapy could prolong overall survival (OS) in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC). Previous studies have shown that radiotherapy can enhance the immunogenicity of tumors, indicating the great potential of combining radiotherapy with immunotherapy. The purpose of this study was to explore the efficacy and safety of adebrelimab combined with chemotherapy and sequential thoracic radiotherapy (TRT) as first-line therapy for ES-SCLC. Methods: Key inclusion factors were 18-75 years old, histologically or cytologically confirmed ES-SCLC, ECOG performance status 0-1, no previous systematic treatment. Pts received 4~6 cycles of adebrelimab (20mg/kg, D1, q3w) combined with EP/EC (etoposide, 100mg/m2, D1-3, q3w and cisplatin, 75mg/m², D1, q3w or carboplatin, AUC = 5, D1, q3w). Pts with response sequentially received adebrelimab combined with consolidate TRT (≥30 Gy in 10 fractions or ≥50 Gy in 25 fractions, involved-field irradiation). Pts then entered the maintenance treatment stage with adebrelimab until disease progression or intolerable side effects. The primary endpoint was OS. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety. Results: From October 2020 to April 2023, 67 pts with ES-SCLC were enrolled. Most patients were male (83.6%), current or former smokers (65.7%) with an ECOG performance status of 1 (95.5%). 22 (32.8%) patients were diagnosed with brain metastasis and 21 (31.3%) patients had liver metastasis at baseline. 45 patients received sequential TRT as planned. All patients were included in the safety and efficacy analysis population. At data cutoff (December 22, 2023), the median follow-up duration was 17.7 months. The median OS was 21.4 months (95% CI: 17.2–not reached months). 1-year and 2-year OS rate were 74.1% (95% CI: 63.6-86.4%) and 39.7% (95% CI: 25.5-61.9%). The median PFS was 10.1 months (95% CI: 6.9–15.5 months). The confirmed ORR was 71.6% (95% CI: 59.3-82.0%) and DCR was 89.6% (95% CI: 79.7-95.7%). The most common grade 3 or higher treatment-related adverse events included neutrophil count decreased (41.8%), white blood cell count decreased (19.4%) and lymphocyte count decreased (13.4%). No unexpected adverse events were observed. Conclusions: Adebrelimab plus chemotherapy and sequential TRT as first-line therapy for ES-SCLC showed promising efficacy and acceptable safety. Clinical trial information: NCT04562337 .

Efficacy and safety of surufatinib, toripalimab, nab-paclitaxel in combination with radiotherapy or surgery in the first-line treatment of esophageal squamous cell cancer: A single-centered prospective clinical trial.

e16047 Background: Chemotherapy(CT) plus immune checkpoint inhibitors (ICIs) has become the current standard of care in the first-line treatment of metastatic esophageal squamous cell cancer(ESCC). In locally advanced setting, radiochemotherapy with or without resection remains the standard of care. Surufatinib, a novel small-molecule kinase inhibitor targeting VEGFR1-3, FGFR and CSF-1R, in combination with PD-1 inhibitors have demonstrated synergistic anti-tumor activities in previous studies. This single-centered prospective clinical trial aims to evaluate the efficacy and safety of surufatinib(SUR), toripalimab(TOR), nab-paclitaxel(NAB) in combination with radiotherapy or surgery in the first-line treatment of locally advanced(LA) or metastatic(R/M) ESCC. Methods: Eligible patients(pts) with confirmed LA or R/M, ECOG PS 0-2 and no prior systematic treatment were enrolled in the trial. Pts would receive 260mg/m2 NAB and TOR 240mg on day 1 and SUR 250mg once daily in each 21-day cycle as induction therapy for two cycles, followed by surgery or another two cycles of concurrent chemoradiotherapy(CCRT) with NAB, SUR and radiotherapy, in which involved-field irradiation were conducted at the dose of 50-63 Gy/25-30F, 1.8-2 Gy per fraction, 5 fractions per week. As maintenance therapy, daily SUR and TOR every three week were administered until disease progression or unacceptable toxicities. Progression-free survival (PFS) was the primary endpoint. Results: As of Jan 7, 2024, 16 pts were enrolled, of whom 15 were evaluable. 14(87.5%) pts were male. The median age was 69.5 (range: 45-79). Tumor located in upper(18.8%), middle(25%) and lower(56.2%) thoracic. 1(6.2%) is Stage II disease, 12(75%) Stage III and 3(18.8%) Stage IV. 8 (50%) pts were with PD-L1 CPS greater than 1, 5 (31.25%) pts greater than 5, and 3 (18.75%) pts greater than 10. PD-L1 CPS of 6(37.50%) pts was unknown. With a median follow-up time of 5 (range: 1-12) months, despite the immatureness of PFS, the 12-month PFS rate was 77.14% (95% CI: 48.89%-100%). The objective response rate was 93.3% (14/15), and disease control rate was 100% (15/15). Five of the included pts met the resection criteria during treatment and underwent subsequent R0 resection. The most common adverse events (≥20%) of all grades were hypoesthesia (62.5%), nausea and vomiting (50%), and white blood cell decrease (43.75%). Conclusions: The combination ofsurufatinib, toripalimab, nab-paclitaxel with radiotherapy or surgery has demonstrated promising efficacy and a well-tolerated safety profile as a potential first-line treatment for LA or R/M ESCC. This ongoing trial merits further investigation and holds significant implications for clinical practice.

Camrelizumab plus chemotherapy combined with consolidative radiotherapy as first-line treatment for oligometastatic esophageal squamous cell carcinoma (ESCORT-1st-RT): A single-arm, open-label, phase 2 trial.

e16043 Background: Compared to chemotherapy alone, immunotherapy combined with chemotherapy as the first-line standard treatment for esophageal squamous cell carcinoma (ESCC) can increase progression-free survival (PFS) to 5.8-7.2 months. This study aimed to explore the feasibility and safety of combining camrelizumab and chemotherapy with consolidative radiotherapy in the treatment of advanced oligometastatic ESCC. Methods: This study included newly diagnosed patients with stage IV ESCC confirmed by histopathology and imaging examination who had ≤ 5 metastatic lesions in ≤ 3 organs. All patients were treated with camrelizumab combined with albumin paclitaxel and carboplatin for 4 cycles, followed by consolidative radiotherapy. The primary esophageal lesion and metastatic lymph nodes were treated with involved-field irradiation therapy, receiving 2.0 Gy per fraction over 25 daily sessions. For distant metastases in organs like the liver, lungs, brain, or bones, radiotherapy was tailored to individual clinical needs, often employing hypofractionated radiation therapy with doses starting at 3 Gy per fraction or above. The maintenance duration of camrelizumab treatment was limited to a maximum of 12 months. The primary endpoint was PFS. The secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 26, 2021, to September 28, 2022, 29 patients with ESCC, median age 63 (range 51-74), were enrolled; 93.1% were male. All had an ECOG score of 0 or 1 and stage IV disease. 27 (93.1%) patients completed planned radiotherapy. Of 29 evaluated patients, 23 achieved an objective response and 6 maintained stable disease. Thus, the ORR and DCR were 79.3% (95% CI 78.2-80.4) and 100% (95% CI 100-100), respectively. With 23.3 months (95%CI 21.5-25.1) of follow-up, the median PFS was13.7 months (95% CI 9.9-17.5) , the median OS has not reached and the 1-year and 2-year OS rates were established at 72.4% (95% CI 52.3-85.1) and 61.4% (95% CI 41.1-76.5), respectively. The most common treatment-emergent adverse events (TEAEs) of grade 3-4 were lymphocyte count decreased (65.5%), neutrophil count decreased (27.6%), and white blood cell count decreased (20.7%). 1 patients discontinued camrelizumab treatment due to radiation esophagitis. No grade 5 TEAEs occurred. Conclusions: Consolidative radiotherapy following camrelizumab combined with chemotherapy showed potential efficacy and manageable tolerability in patients with advanced oligometastatic ESCC.

Involved-field radiotherapy in older patients with superficial thoracic esophageal squamous cell carcinoma: long-term outcomes and recurrence patterns

PurposeAn optimal radiotherapy field for superficial esophageal carcinoma is yet to be established. We evaluated the long-term outcomes and recurrence patterns of involved-field radiotherapy (IFRT) in older patients with superficial thoracic esophageal squamous cell carcinoma (ESCC).Materials and methodsFifty-four patients (49 men and 5 women; mean age, 77 [range: 66–90] years) who underwent IFRT for superficial thoracic ESCC between January 2003 and January 2019 were retrospectively reviewed. Concurrent chemotherapy was administered at the discretion of the attending physician. The primary endpoint was overall survival. The secondary endpoints were progression-free survival and complete response rate.ResultsThe tumors were localized in the upper, middle, and lower thoracic esophagus in 2, 40, and 12 patients, respectively. All patients underwent IFRT using anteroposterior and anterior–posterior oblique opposed beams (off-cord). The prescribed total doses were 50.4, 59.4–61.2, and 66–70 Gy for 6, 40, and 8 patients, respectively. Concurrent chemotherapy was administered to 33 patients. The median follow-up duration was 57 months. The median overall survival was 115 months. The 5-year overall and progression-free survival rates were 71.7% and 60.1%, respectively. Forty-nine patients had a complete response at one month after IFRT (complete response rate: 90.7%). Twenty patients had recurrence; there were 13 in-field and 7 out-of-field recurrence cases. The radiation-related adverse events were generally mild. Grade 3 late toxicity was observed in one patient.ConclusionsThe efficacy of IFRT was suggested to be comparable to that of standard treatments. Therefore, IFRT can be a promising approach for treating superficial ESCC in older adults, especially those with severe comorbidities.

Involved-site Radiation Therapy is Equally Effective and Less Toxic Than Involved-field Radiation Therapy in Patients Receiving Combined Modality Treatment for Early-stage Unfavorable Hodgkin Lymphoma—An Analysis of the Randomized Phase 3 HD17 Trial of the German Hodgkin Study Group

PurposeCombined modality treatment (CMT) with chemotherapy followed by consolidation radiotherapy (RT), provides excellent outcomes for patients with early-stage Hodgkin lymphoma (HL). The international standard of care for consolidation RT, involved-site/involved-node radiotherapy (ISRT/INRT), has never been evaluated in a randomized phase III trial against the former standard involved-field radiotherapy (IFRT). Methods and materialsIn the multicenter phase III AnonymizedStudyGroupXXX AnonymizedStudyYYY trial, patients with early stage unfavorable HL were randomized between the standard CMT group and a positron-emission tomography (PET) -guided group. In the standard group, patients received two cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) and two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gray (Gy) IFRT. In the experimental group patients received no further therapy if post-chemotherapy PET was negative, and 30 Gy AnonymizedStudyGroupXXX -INRT, comparable and therefore termed here ISRT, if PET was positive. Here, we analyze the interim PET positive patients in a post hoc analysis, and therefore the randomized comparison of IFRT versus INRT/ISRT. Results1,100 patients were randomized, of which 311 had a positive PET after chemotherapy. Kaplan-Meier estimates of 4-year progression-free survival (PFS) were 96.8 % (95% CI: 91.6% – 98.8%) in the IFRT group and 95.4% (95% CI: 89.9% – 97.9%; HR: 1.40, 95% CI: 0.44 – 4.42) in the ISRT group. Pattern of recurrence analyses indicated that none of the cases of disease progression or recurrence in the ISRT group would have been prevented by the use of IFRT. Acute grade III/IV toxicities occurred in 8.5% of IFRT patients and 2.6% of ISRT patients (p=0.03). ConclusionsFor the first time, consolidation INRT/ISRT was randomly compared to IFRT in a phase III trial. Regarding PFS, no advantage for IFRT could be demonstrated. In summary, our data confirm the place of INRT/ISRT as the current standard of care.

Long-Term Results of IFRT vs. ISRT in Infradiaphragmal Fields in Aggressive Non-Hodgkins’s Lymphoma Patients—A Single Centre Experience

(1) Background: This study aimed to examine the difference in efficacy and toxicity of involved-field (IFRT) and involved-site radiotherapy (ISRT) fields in infradiaphragmal aggressive non-Hodgkin lymphoma patients. (2) Methods: In total, 140 patients with infradiaphragmal lymphoma treated between 2003 and 2020 were retrospectively evaluated. There were 69 patients (49%) treated with IFRT, and 71 (51%) patients treated with ISRT. The median dose in the IFRT group was 36 Gy, (range 4–50.4 Gy), and in the ISRT group, it was 30 Gy (range 4–48 Gy). (3) Results: The median follow-up in the IFRT group was 133 months (95% CI 109–158), and in the ISRT group, it was 48 months (95% CI 39–57). In the IFRT group, locoregional control was 67%, and in the ISRT group, 73%. The 2- and 5-year overall survival (OS) in the IFRT and ISRT groups were 79% and 69% vs. 80% and 70%, respectively (p = 0.711). The 2- and 5-year event-free survival (EFS) in the IFRT and ISRT groups were 73% and 68% vs. 77% and 70%, respectively (p = 0.575). Acute side effects occurred in 43 (31%) patients, which is more frequent in the IFRT group, 34 (39%) patients, than in the ISRT group, 9 (13%) patients, p > 0.01. Late toxicities occurred more often in the IFRT group of patients, (10/53) 19%, than in the ISRT group of patients, (2/37) 5%, (p = 0.026). (4) Conclusions: By reducing the radiotherapy volume and the doses in the treatment of infradiaphragmatic fields, treatment with significantly fewer acute and long-term side effects is possible. At the same time, efficiency and local disease control are not compromised.

The implication of failure patterns after neoadjuvant chemoradiotherapy with small involved-field in esophageal squamous cell carcinoma.

376 Background: In this study, we aimed to analyze failure patterns, the clinical and biological prognostic factors for treatment outcomes, and evaluate the feasibility of involved-field irradiation (IFI) in patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (CCRT). Methods: We retrospectively reviewed the medical records of 511 patients diagnosed with ESCC and underwent neoadjuvant CCRT and radical esophagectomy between January 2016 and February 2022 at Samsung Medical Center. For IFI, the clinical target volume (CTV) was defined as the primary gross tumor volume (GTV) plus a 2.0-3.0 cm longitudinal margin and a 0.5-1.0 cm circumferential margin, as well as the GTV of lymph nodes (LN) plus a 0.5-1.0 cm margin. For elective nodal irradiation (ENI), the CTV encompassed supraclavicular, mediastinal, or abdominal LN regions based on the primary tumor location. IFI was applied in most cases (98%). The failure patterns, loco-regional control (LRC), and survival outcome were analyzed. Regional lymph nodes (LNs) were defined and classified according to the AJCC 8th edition. Non-regional LNs were defined as metastatic LNs in neck, thorax, abdominal area except regional LNs. Results: With a median follow-up of 44.4 months, 213 (41.7%) patients experienced recurrence. The first recurrent sites were locoregional (LR) in 98 patients (19.2%), non-regional LN in 81 (15.9%), and distant organs in 152 (29.7%). Among the 98 patients with LR recurrence, RT in-field failure occurred in 53 (10.4%) patients, in & out-field failure in 18 (3.5%), and out-field failure in 27 (5.3%). In 27 cases of out-field failure only, LR recurrent lesion could be included in the target volume in 7 (1.4%) cases if ENIs were applied. Among the 27 patients, 10 received salvage treatment and 2 did not experience further recurrence. The analysis for the detailed LN recurrence showed that the upper mediastinal and supraclavicular LNs were the most frequent area, regardless of the primary tumor location and other clinical factors. Among 213 recurrent cases, 54 (10.5%) recurred in upper paratracheal LN and 40 (7.8%) in supraclavicular LN. The 5-year LRC rates, disease-control rates, and overall survival (OS) rates were 77.5%, 53%, and 54.3%, respectively. Multivariate analysis revealed that gender, age, cStage, ypStage, and resection margin status were independent prognostic factors for OS. Conclusions: Neoadjuvant CCRT using IFI with a small margin showed favorable treatment outcomes and out-field recurrence that the traditional ENI field could cover accounted for a small portion; thus, it might be feasible in the neoadjuvant setting. However, we need to consider that the upper mediastinal and supraclavicular areas were the most frequent recurrence sites.

Definitive chemo-radiotherapy in cervical oesophageal cancer: a comprehensive review of literature.

Despite decades of experience with definitive chemo-radiotherapy (CRT) in cervical oesophageal cancer (CEC), the loco-regional control and survival outcomes are dismal. This review evaluated the outcomes of various treatment strategies being commonly utilized. A literature review was conducted to identify relevant articles on CEC published from years 2000-2023 addressing the predefined key questions. These questions focussed on the comparative outcomes of various primary treatment approaches (surgery, CRT, or trimodality treatment) and the radiation dose schedules, volumes, and techniques. CRT is the standard approach for treatment for CEC so far. The potential role of surgery and trimodality approach in settings of evolving surgical approaches needs to be validated. The high dose schedules that are preferentially practiced in CEC have not shown any benefit in improving the disease outcomes over the standard dose schedule of 50.4 Gy. The target volume delineation practice of elective nodal irradiation (ENI) does not have a proven benefit over the involved field irradiation (IFI). The limited evidence on radiation techniques suggests that intensity-modulated radiotherapy/volumetric-modulated arc therapy (IMRT/VMAT) techniques can improve toxicity profile over three-dimensional conformal radiotherapy (3DCRT), but no advantage proven in disease outcomes so far. This review will guide clinicians in decision-making for the management of this relatively rare entity and the directions for future research in these areas. Future large-scale multicentre prospective studies are needed for validating and standardizing our current practices and exploring potential options to improve the outcomes.

Safety and early efficacy of involved-field SBRT for nodal oligo-recurrent prostate cancer.

Following treatment for localized prostate cancer, a subset of men will develop recurrent disease in the abdominopelvic nodes. For radiation therapy (RT), the optimal treatment volume, fractionation schedule, and dose remain unanswered questions. We report early outcomes for patients treated with involved-field stereotactic body radiation therapy (SBRT) (IF-SBRT) for nodal oligo-recurrent (NOR) prostate cancer. Between January 2018 and October 2023, 67 patients with a median age of 75 with NOR prostate cancer treated with 74 courses of IF-SBRT at Georgetown were eligible for this analysis. NOR was defined as any volume of disease that could be safely treated within an IF. All patients were treated with five-fraction IF-SBRT (27.5-35 Gy). The IF treatment volume was defined as the nodal basin containing the gross disease as well as the immediately adjacent basins. Disease progression was defined as a prostate-specific antigen (PSA) rise above the pretreatment baseline or initiation of a second treatment. Local control and progression-free survival were calculated using the Kaplan-Meier method. Detection of pre-SBRT NOR was ascertained by prostate-specific membrane antigen (PSMA) (38%), fluciclovine (50%), or MRI/CT (12%). Median follow-up was 50 months (1-262). The median pre-salvage PSA was 6.5 ng/mL (range, 0.1-335). The median number of involved nodes was 3 (range, 1-16). The local control at 1 and 2 years was 98% and 93%, respectively. The 1- and 2-year progression-free survival was 78% and 50%, respectively. Twenty percent of treatment courses were followed by acute Grade 2 gastrointestinal (GI) toxicity: diarrhea (9%) and/or nausea (14%). Two patients (3%) experienced late Grade 2 nausea. On univariate analysis, measures of disease volume such as hormone sensitivity (p = 0.03), increasing involved node number (p = 0.008), and abdominal treatment (p = 0.03) were significantly associated with GI toxicity. With the widespread adoption of PSMA agents, NORs are likely to increase. The optimal combination of local and systemic therapy in this population is unknown. With a favorable toxicity profile, IF-SBRT represents a safe and convenient local therapy treatment option for an elderly patient population. Patient- and treatment-related factors such as a large number of involved nodes and/or abdominal treatment may be associated with an increased risk of GI toxicity.

Motion Management: The Road Map to Accurate Radiation Treatment Delivery

Radiation therapy is a key contributor to positive outcomes in hematological malignancies. However, this is contingent on minimizing the exposure of critical normal organs. The introduction of computed tomography (CT) for radiation treatment planning and the development of sophisticated dose calculation algorithms has transformed the radiation therapy field and made it possible to transition from conventional involved-field radiation to modern involved-site radiation therapy. Thanks to rapid advances in drug discovery, treatment strategies for many hematological malignancies have evolved to incorporate targeted and cellular therapies, in some cases even allowing the replacement of chemotherapy. As a result, new opportunities have been created for radiation to address relapses after more lines of therapy, identify disease-involving sanctuary sites, and bridge to the subsequent therapy. When considering radiation in patients receiving novel therapies, who may also be more heavily pretreated, respecting the critical and normal structures at all costs is imperative. In this document, we will describe modern techniques used to deliver state-of-the-art radiation therapy and practical considerations to ensure the accurate treatment of the target while avoiding normal organs at risk.

A comparative study of elective nodal irradiation and involved field irradiation in elderly patients with advanced esophageal cancer.

This comparative study aimed to explore the feasibility of involved field irradiation (IFI) in the radiotherapy of elderly patients with advanced esophageal cancer, compared with elective nodal irradiation (ENI). A total of 245 elderly patients (age ≥70 years) with advanced esophageal cancer, who received radiotherapy in our department from January 2014 to December 2020, were divided into the ENI group (n=111) and the IFI group (n=134). Clinical efficacy, toxicities, survival rates, treatment failures, and multifactorial survival analyses were conducted for both groups. The ENI group and the IFI group showed no significant differences in terms of short-term efficacy (91.9% vs 91.0%, P=0.814), 1-year overall survival (OS) (81.1% vs 74.6%, P=0.228), 2-year OS (22.5% vs 25.4%, P= 0.603), 1-year progression-free survival (PFS) (56.8% vs 51.5%, P= 0.198), 2-year PFS (8.1% vs 9.0%, P=0.814), regional failures (38.7% vs 31.3%, P=0.226), and distant metastasis (21.6% vs 14.9%, P=0.174). The median overall survival (OS) was 19 months in the ENI group and 18 months in the IFI group (Log-rankχ 2=0.012, P=0.913). The median progression-free survival (PFS) was 13 months in the ENI group and 11 months in the IFI group (Log-rankχ 2=1.834, P=0.176). There were no significant statistical differences in both OS and PFS (P>0.05). The incidence of grade ≥3 radiation pneumonia and grade ≥3 radiation esophagitis in the IFI group was 8.2% and 11.2%, respectively, which were significantly lower than those in the ENI group (17.1%, P=0.034; 21.6%, P=0.026). Univariate analysis revealed that age, gender, T stage, N stage, and synchronous chemotherapy were factors affecting prognosis. Multivariate analysis showed that age, gender, T stage, and synchronous chemotherapy were independent prognostic factors, with hazard ratios of 1.227, 1.466, 2.441, and 2.714, and P values of <0.001, 0.006, <0.001, and<0.001, respectively. IFI is a suitable choice for elderly patients with advanced esophageal cancer, as it yields similar efficacy to ENI while reducing toxicities. Age, gender, T stage, and synchronous chemotherapy are independent prognostic factors for elderly patients with esophageal cancer.

Treatment of high-risk Hodgkin lymphoma with a modified Stanford V regimen in the AHOPCA: Substituting chemotherapy agents and hampered outcomes.

High-risk Hodgkin lymphoma (HRHL) in children is curable with combined modality therapy. The Association of Pediatric Hematology-Oncology of Central America (AHOPCA) is a consortium of cancer centers from Central America. In 2004, AHOPCA implemented a guideline with a short course of chemotherapy (mStanfordV), strict diagnostics, and radiation guidelines, aimed at reducing abandonment and improving outcomes. Newly diagnosed children less than 18years of age with high-risk HL (Ann Arbor stages: IIB, IIIB, IV) from AHOPCA centers were staged with chest radiography and ultrasound or computed tomography. Therapy was a modified Stanford V (mStanfordV), substituting cyclophosphamide for mechlorethamine and involved field radiation. Of 219 patients with HRHL, 181 patients were eligible and evaluable; 146 (81%) were boys, 22% being less than 6years; 43 were stage IIB, 84 IIIB, and 54 IV. Thirty-one (17%) abandoned therapy, 28 (15%) progressed, 30 (17%) relapsed, and eight (4%) died of toxicity. Radiation guidelines were not followed. Five-year abandonment-sensitive event-free survival and overall survival (AS-EFS, AS-OS±SE) for the cohort were 46%±4% and 56%±4%; 5-year AS-OS for stages IIB, IIIB, and IV was 76%±7%, 59%±7%, and 35%±7% (p=.0006). Despite instituting a short treatment guideline, it did not improve the abandonment rate (17%) and did not achieve the reported outcomes of Stanford V. The cyclophosphamide dose used to replace merchlorethamine was inadequate. Despite strict guidelines, the radiation therapy application was inaccurate. Weekly chemotherapy may have adversely affected abandonment of therapy by increasing the burden of travel time. Based on these results, AHOPCA established a new abandonment strategy and a new guideline.

Performance of Positron Emission Tomography at Diagnosis and Response Assessment in Low and Intermediate-Risk Nodular Lymphocyte Predominant Hodgkin Lymphoma

Background: Nodular lymphocyte predominant Hodgkin lymphoma (nLPHL) has different histology, clinical presentation, and outcomes than classical Hodgkin Lymphoma (cHL). Positron Emission Tomography (PET) plays an important role in staging and response assessment in cHL, but little is published about the use of PET to guide treatment in nLPHL. A better understanding of the clinical significance of PET response in nLPHL is critical for incorporating PET into prospective trials. Methods: Children's Oncology Group study AHOD03P1 (NCT00107198) enrolled patients with low-risk nLPHL and AHOD0031 (NCT00025259) enrolled patients with intermediate-risk cHL and nLPHL &amp;lt;22 years of age. AHOD03P1 patients with stage IA and &amp;gt;1 lymph node or stage IIA nLPHL were treated with 3 cycles of doxorubicin, vincristine, prednisone, and cyclophosphamide (AV-PC) chemotherapy, given every 21 days. Patients with a complete response (CR) based on anatomic response and qualitative reading (&amp;lt;mediastinal blood pool) of negative PET on central review did not receive radiation therapy while patients with &amp;lt;CR received 21-Gy involved field radiation therapy (IFRT). AHOD0031 patients with stages IB, IAE, IIB, IIAE, IIIA, IVA with or without bulk disease, and IA or IIA with bulk disease received 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide (ABVE-PC) followed by response evaluation. Slow early responders were randomized to an additional 2 cycles of ABVE-PC with or without 2 cycles of dexamethasone, etoposide, cisplatin and cytarabine (DECA) and all received IFRT. Rapid early responders (RERs) received 2 additional cycles of ABVE-PC. RERs with CR were randomized to IFRT or no further therapy. RER/non-CRs were non-randomly assigned to IFRT. PET scans from both trials available in the Imaging and Radiation Oncology Core (IROC) were retrospectively reviewed and assigned a score of 1-5 on the Deauville 5-point scale (5PS). Patients who did not have evaluable imaging due to either scans not performed, on CD-ROM and inaccessible, or poor quality, were excluded from this analysis. Three-year event-free survival (EFS) was analyzed by 5PS at end of therapy using the Kaplan Meier method. Results: AHOD03P1 enrolled 135 patients with low-risk nLPHL who received chemotherapy and AHOD0031 enrolled 96 patients with intermediate-risk nLPHL. PET imaging available for review at diagnosis in 99 low-risk patients, 92% 5PS=5, and 55 intermediate-risk patients, 98% 5PS=5. Median age 13.4 years (range 16.5), 84.9% male, 29.9% Stage I, 49.8% Stage II, 18.6% Stage III, and 1.7% Stage IV. After 3 cycles of chemotherapy, 106 low-risk patients had available PET scans, 5PS 1 n=50, 5PS 2 n=35, 5PS 3 n=11, 5PS 4 n=7, and 5PS 5 n=3. Three-year EFS for patients with end of chemotherapy 5PS was: 5PS 1 89.9% (95% CI 77.3-95.7%), 5PS 2 97.1% (95% CI 81.4-99.6%), 5PS 3 90.9% (95% CI 50.8-98.7%), 5PS 4 28.6% (95% CI 1.0-71.1%), 5PS 5 66.7% (95% CI 5.4-94.5%) p=0.0081. When categorized as PET negative (5PS 1-3) and PET positive (5PS 4-5), 3-year EFS was 92.6% (95% CI 85.2-96.4%) for PET negative and 45.0% (95% CI 10.6-75.3%) for PET positive patients, p=0.0036 (Figure 1A). Forty-nine intermediate-risk patients had available PET scans after 2 cycles of chemotherapy, 5PS 1 n=9, 5PS 2 n=26, 5PS 3 n=10, 5PS 4 n=3, and 5PS 5 n=1. Three-year EFS by interim response was: 5PS 1 88.9% (95% CI 43.3-98.4%), 5PS 2 96.0% (95% CI 74.8-99.4%), 5PS 3 100%, 5PS 4 100%, 5PS 5 0%, p&amp;lt;0.0001. Thirty-six patients had available PET scans after 4 cycles of chemotherapy, 5PS 1 n=20, 5PS 2 n=11, 5PS 3 n=3, 5PS 4 n=1, and 5PS 5 n=1. Three-year EFS by response after 4 cycles of chemotherapy: 5PS 1 95.0% (95% CI 69.5-99.3%), 5PS 2 100%, 5PS 3 100%, 5PS 4 100%, 5PS 5 0% p&amp;lt;0.0001. When divided into PET negative (5PS 1-3) and PET positive (5PS 4-5), 3-year EFS 97.0% (95% CI 80.4-99.6%) for PET negative and 50.0% (95% CI 0.6-91.0%) for PET positive patients after 4 cycles of chemotherapy, p=0.1449 (Figure 1B). Conclusions: At diagnosis, low and intermediate-risk nLPHL lesions are almost always PET avid with 5PS=5. PET response following 3 cycles of AV-PC chemotherapy is highly predictive of outcome in pediatric patients with low-risk nLPHL when considering 5PS=3 as PET negative. Intermediate-risk patients with negative PET following ABVE-PC achieved excellent outcomes. Whether PET maintains prognostic significance in patients with nLPHL treated with rituximab needs to be studied.