Adaptive IMRT Research Articles

Optimizing Treatment Quality in Head and Neck Cancer Therapy: Impact of Adaptive Intensity-Modulated Radiotherapy on Plan Quality and Tumor Volume Changes

Objective: This research analyses whether volumetric changes and PTV shifting affect adaptive intensity-modulated radiotherapy (IMRT) plan quality and head and neck cancer therapy. Methods: The research was carried out at the Sohag Cancer Centre in Egypt, including a sample of 36 individuals diagnosed with head and neck squamous cell carcinoma (HNSCC). Patients were chosen on the basis of the following criteria: locally progressed and node-positive malignancy, oropharyngeal cancer, oral cavity cancer, and unknown primary. The research used dynamic intensity-modulated radiation therapy (D-IMRT) to establish treatment plans and Siemens SOMATOM DEFINITION CT scanners to acquire 3D anatomical images. A range of 1.64 to 2.12 Gy was observed for the median dosage per fraction. Using the conformance index (CI) and the homogeneity index, the quality of the plan was assessed (HI). The threshold for statistical significance was set at 0.05. Results: The study analysed patients with unilateral and bilateral HNSCC tumors, with a majority having bilateral tumors. The findings demonstrated that the tumor PTV was significantly reduced as a consequence of the suggested adaptive radiation techniques. Both the homogeneity index and the conformity index were used to evaluate the plan's quality (HI). The maximal homogeneity index (HI) was reached after 7 and 14 fractions, respectively. The positive correlation between PTV reduction and CI after 7 fractions, while a negative correlation found after fractions 14 and 21. It was also shown that HI is positively correlated with PTV changes after 7 and 14. Conclusion: The use of adaptive radiotherapy in intensity-modulated radiation therapy (IMRT) treatment planning improves plan quality and decreases error rates due to tumor margin movement. Following radiation fractions, PTV shifting affects the homogeneity index (HI).

Reducing Salivary Toxicity with Adaptive Radiotherapy (ReSTART): A Randomized Controlled Trial Comparing Conventional IMRT to Adaptive IMRT in Head and Neck Squamous Cell Carcinomas

BackgroundThe utility of Adaptive Radiotherapy (ART) in Head and Neck Squamous Cell Carcinoma (HNSCC) remains to be ascertained. While multiple retrospective and single-arm prospective studies have demonstrated its efficacy in decreasing parotid doses and reducing xerostomia, adequate randomized evidence is lacking. Methods and AnalysisReSTART (Reducing Salivary Toxicity with Adaptive Radiotherapy) is an ongoing phase III randomized trial of patients with previously untreated, locally advanced HNSCC of the oropharynx, larynx, and hypopharynx. Patients are randomized in a 1:1 ratio to the standard Intensity Modulated Radiotherapy (IMRT) arm {Planning Target Volume (PTV) margin 5 mm} vs. Adaptive Radiotherapy arm (standard IMRT with a PTV margin 3 mm, two planned adaptive planning at 10th and 20th fractions). The stratification factors include the primary site and nodal stage. The RT dose prescribed is 66Gy in 30 fractions for high-risk PTV and 54Gy in 30 fractions for low-risk PTV over six weeks, along with concurrent chemotherapy.The primary endpoint is to compare salivary toxicity between arms using salivary scintigraphy 12 months' post-radiation. To detect a 25% improvement in the primary endpoint at 12 months in the ART arm with a two-sided 5% alpha value and a power of 80% (and 10% attrition ratio), a sample size of 130 patients is required (65 patients in each arm). The secondary endpoints include acute and late toxicities, locoregional control, disease-free survival, overall survival, quality of life, and xerostomia scores between the two arms. DiscussionThe ReSTART trial aims to answer an important question in Radiation Therapy for HNSCC, particularly in a resource-limited setting. The uniqueness of this trial, compared to other ongoing randomized trials, includes the PTV margins and the xerostomia assessment by scintigraphy at 12 months as the primary endpoint.

Comparing Predicted Toxicities between Hypofractionated Proton and Photon Radiotherapy of Liver Cancer Patients with Different Adaptive Schemes.

With the availability of MRI linacs, online adaptive intensity modulated radiotherapy (IMRT) has become a treatment option for liver cancer patients, often combined with hypofractionation. Intensity modulated proton therapy (IMPT) has the potential to reduce the dose to healthy tissue, but it is particularly sensitive to changes in the beam path and might therefore benefit from online adaptation. This study compares the normal tissue complication probabilities (NTCPs) for liver and duodenal toxicity for adaptive and non-adaptive IMRT and IMPT treatments of liver cancer patients. Adaptive and non-adaptive IMRT and IMPT plans were optimized to 50 Gy (RBE = 1.1 for IMPT) in five fractions for 10 liver cancer patients, using the original MRI linac images and physician-drawn structures. Three liver NTCP models were used to predict radiation-induced liver disease, an increase in albumin-bilirubin level, and a Child-Pugh score increase of more than 2. Additionally, three duodenal NTCP models were used to predict gastric bleeding, gastrointestinal (GI) toxicity with grades >3, and duodenal toxicity grades 2-4. NTCPs were calculated for adaptive and non-adaptive IMRT and IMPT treatments. In general, IMRT showed higher NTCP values than IMPT and the differences were often significant. However, the differences between adaptive and non-adaptive treatment schemes were not significant, indicating that the NTCP benefit of adaptive treatment regimens is expected to be smaller than the expected difference between IMRT and IMPT.

High-dose planned adaptive helical tomotherapy for cutaneous angiosarcoma of the scalp.

The purpose of this study was to investigate the feasibility and effectiveness of high-dose planned adaptive intensity-modulated radiation therapy (IMRT) with helical tomotherapy (HT) for cutaneous angiosarcoma (cAS) of the scalp. This retrospective cross-sectional included atotal of 12consecutive patients with cAS of the scalp who underwent high-dose planned adaptive IMRT with HT. Prescribed doses were 72.5-74 Gy in 35-37 fractions for the gross tumor volume plus a1-2 mm margin (PTV1), 58-60 Gy in 29-30 fractions for the clinical target volume plus a2-3 mm margin (PTV2), and 46 Gy in 23fractions for the clinical target volume plus a5-15 mm margin (PTV3) over periods of 7.5, 6and 4.5weeks, respectively. The estimated 1‑year and 2‑year overall survival rate were 65.6% and 27.3%, respectively, and the local progression-free survival at 2years was 74.1%. All local recurrences were either in or marginal to the PTV2 or PTV3. No local recurrence was observed in the PTV1. All patients tolerated the treatment without grade3 or higher adverse events during the radiotherapy period. No late adverse events were observed during the follow-up period. Planned adaptive high-dose IMRT with HT has the potential to improve local control rate without increasing adverse events.

Comparison of Online-Onboard Adaptive Intensity-Modulated Radiation Therapy or Volumetric-Modulated Arc Radiotherapy With Image-Guided Radiotherapy for Patients With Gynecologic Tumors in Dependence on Fractionation and the Planning Target Volume Margin

Patients with newly diagnosed locally advanced cervical carcinomas or recurrences after surgery undergoing radiochemotherapy whose tumor is unsuited for a brachytherapy boost need high-dose percutaneous radiotherapy with small margins to compensate for clinical target volume deformations and set-up errors. Cone-beam computed tomography-based online adaptive radiotherapy (ART) has the potential to reduce planning target volume (PTV) margins below 5 mm for these tumors. To compare online ART technologies with image-guided radiotherapy (IGRT) for gynecologic tumors. This comparative effectiveness study comprised all 7 consecutive patients with gynecologic tumors who were treated with ART with artificial intelligence segmentation from January to May 2022 at the West German Cancer Center. All adapted treatment plans were reviewed for the new scenario of organs at risk and target volume. Dose distributions of adapted and scheduled plans optimized on the initial planning computed tomography scan were compared. Online ART for gynecologic tumors. Target dose coverage with ART compared with IGRT for PTV margins of 5 mm or less in terms of the generalized equivalent uniform dose (gEUD) without increasing the gEUD for the organs at risk (bladder and rectum). The first 10 treatment series among 7 patients (mean [SD] age, 65.7 [16.5] years) with gynecologic tumors from a prospective observational trial performed with ART were compared with IGRT. For a clinical PTV margin of 5 mm, IGRT was associated with a median gEUD decrease in the interfractional clinical target volume of -1.5% (90% CI, -31.8% to 2.9%) for all fractions in comparison with the planned dose distribution. Online ART was associated with a decrease of -0.02% (90% CI, -3.2% to 1.5%), which was less than the decrease with IGRT (P < .001). This was not associated with an increase in the gEUD for the bladder or rectum. For a PTV margin of 0 mm, the median gEUD deviation with IGRT was -13.1% (90% CI, -47.9% to 1.6%) compared with 0.1% (90% CI, -2.3% to 6.6%) with ART (P < .001). The benefit associated with ART was larger for a PTV margin of 0 mm than of 5 mm (P = .004) due to spreading of the cold spot at the clinical target volume margin from fraction to fraction with a median SD of 2.4 cm (90% CI, 1.9-3.4 cm) for all patients. This study suggests that ART is associated with an improvement in the percentage deviation of gEUD for the interfractional clinical target volume compared with IGRT. As the gain of ART depends on fractionation and PTV margin, a strategy is proposed here to switch from IGRT to ART, if the delivered gEUD distribution becomes unfavorable in comparison with the expected distribution during the course of treatment.

Induction chemotherapy reduces target volume drift in patients with locoregionally advanced nasopharyngeal carcinoma undergoing adaptive intensity-modulated radiotherapy: a retrospective cohort study.

Adaptive radiotherapy (ART) provides real-time correction of the target and dose of radiation based on repeat computed tomography (CT) imaging and replanning during intensity-modulated radiation therapy (IMRT) and is important for locoregionally advanced nasopharyngeal carcinoma (NPC). However, repeat CT imaging and replanning are time-consuming and hinder the broader application of ART. The optimum dose and frequency of replanning time have been published in previous reports. The purpose of this study was to determine whether induction chemotherapy (IC) reduces target volume drift during IMRT, potentially reducing the replanning workload. From January 2012 to December 2017, 40 patients with locoregionally advanced, nonmetastatic stage III-IVa NPC treated in the Department of Radiation Oncology in the First Affiliated Hospital, College of Medicine, Zhejiang University, were enrolled into this study. Of the 40 patients, 20 received 2-3 cycles of IC before concurrent chemoradiotherapy (IC + CCRT), and the other 20 patients were treated with CCRT plus adjuvant chemotherapy (CCRT + AC). During CCRT, all patients underwent weekly simulated CT for 6 weeks. The gross tumor volume (GTV), clinical target volume (CTV), and body weight were measured weekly and compared between the 2 groups. Compared with the baseline, the mean weight loss after 25 fractions was 7.0 kg (13.6%; range, 3.9-25.5%) in the CCRT + AC group and 5.7 kg (8.3%; range, 3.6-20%) in the IC + CCRT group. The mean GTV and CTV decreased by 16.55 mL (15.7%; range, 6.1-33.7%) and 61.25 mL (9.33%; range, 4.4-17.0%), respectively, in the IC + CCRT group, and by 39.86 mL (38.79%; range, 25.3-50.7%) and 87.72 mL (12.7%; range, 6.7-22.9%), respectively, in the CCRT + AC group. The degree of weekly reduction in the GTV of the IC + CCRT group was not significantly higher than that of the CCRT + AC group, with the following P values of each percentage reduction in comparison with the previous week over 5 weeks, respectively: P<0.001, P=0.015, P=0.01, P=0.01, and P<0.001. The weekly CTV reduction only significantly correlated with weight loss (P=0.005) in the IC + CCRT group. IC significantly decreased the degree of weight loss, GTV shrinkage, and CTV reduction during CCRT, consequently decreasing the anatomical and target dose drift during the adaptive replanning of IMRT. This may lead to a reduction in the recurrence of locoregionally advanced NPC, especially among patients with large metastatic cervical lymph nodes, potentially improving survival. This result provides favorable evidence that IC improves locoregional recurrence-free survival (LRFS) and overall survival (OS) in patients with locoregionally advanced NPC.

SURVIVAL AND LONGTERM TOXICITIES OUTCOMES IN ADAPTIVE INTENSITY-MODULATED RADIOTHERAPY (ART) VS IMRT IN LOCALLY ADVANCED HEAD AND NECK CANCER.

Background: Anatomic complexity is a challenge for radiation oncologist.Repeated CT scans and replanning can overcome the variations in terms of size or shape a tumour has undergone during treatment , this process has been termed as Adaptive Radiotherapy(ART). The use of adaptive approach or IMRT-SIB is still under debate since there is not enough evidence of long-term clinical outcomes , metastasis free survival. Total Sixty patients Materials And Methods: with locally advanced HNC with a intent to cure were assigned into two arms to receive IMRT up to a dose of 70 Gy with concurrent weekly chemotherapy and were prospectively analyzed between March 2018 and March 2019. Repeat CT scan was acquired after the 3rd week of radiation and those in the study arm were replannned and those in the controlarm continued with the rst IMRT plan. For the entire cohort, patients were assessed weekly till the end of treatment and at 1, 3, and6 months, 1 year and 2 years thereafter. Main focus was on Xerostomia status at end of 6 months and end of 2 years and Survival (OS) rates at end of 2-years was calculated and hence compared. 2 years overall survival rate wa Results: s almost similar with 73.33% vs 76.66% in adaptive IMRTand conventional IMRT respectively; p value= 0. 23 Xerostomia was statistically signicantly higher in the conventional arm at 6 months(p=0.01).Grade ≥II xerostomia at end of 2 years reduced to 0% vs 4.43 %in adaptive and conventional IMRT respectively (p= 0.78). Conclusion: Adaptive IMRT can help to minimise xerostomia at end of 6 months .However no major benet in survival when compared 2 year after completion of treatment.

Magnetic resonance imaging-guided high-dose planned adaptive intensity-modulated radiation therapy for locally advanced cervical cancer

Magnetic resonance imaging-guided radiotherapy can accurately irradiate moving targets such as cervical cancer. An 82-year-old woman with locally advanced cervical cancer was referred for palliative radiotherapy. She had refused chemotherapy and brachytherapy, so she was treated with external beam radiotherapy to control her uterine bleeding and to alleviate pubic pain. Since her cervical cancer had no metastases, and she was expected to survive for a long time, curative doses of radiation (70–80 Gy/28 fractions) were administered by magnetic resonance imaging-guided planned adaptive intensity-modulated radiation therapy. Six months after intensity-modulated radiation therapy, the tumor disappeared without adverse events, and her symptoms were relieved. To the best of our knowledge, this is the first report of locally advanced cervical cancer treated with high-dose magnetic resonance imaging-guided adaptive intensity-modulated radiation therapy.

High-dose planned adaptive intensity-modulated radiation therapy with simultaneous integrated boost for synchronous oligometastatic pancreatic cancer.

The purpose of this study was to investigate the efficacy and feasibility of high-dose (72.6 Gy) planned adaptive intensity modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB) for 9 consecutive patients with synchronous oligometastatic pancreatic ductal adenocarcinoma (PDAC). The estimated 2-year overall survival rate was 66.7%, and the local progression-free survival at 2 years was 83.3%. No severe adverse events were observed. Planned adaptive dose-escalated IMRT-SIB has the potential to improve local control rate and prolong overall survival in patients with synchronous oligometastatic PDAC.

Dosimetric comparison of MR-guided adaptive IMRT versus 3DOF-VMAT for prostate stereotactic radiotherapy.

To compare the dosimetry of prostate stereotactic radiotherapy (SBRT) delivered by adaptive intensity modulated radiotherapy (A-IMRT) and 3 degree of freedom volumetric modulated arc therapy (3DOF-VMAT). Twenty-five prostate patients treated with High Dose Rate (HDR) brachytherapy followed by SBRT were included (fifteen with hydrogel spacer in place for treatment). Interfraction changes in the volume of prostate, rectum and bladder were measured. Fractional dose to these structures was estimated for A-IMRT and 3DOF-VMAT for comparison against the corresponding reference dose and between each other. Clinically acceptable dose was delivered to prostate in all 125 fractions through A-IMRT and 3DOF-VMAT. A-IMRT was better than 3DOF-VMAT in reducing dose to 1cm3 of rectum. Conversely, 3DOF-VMAT was superior in sparing 50% and 20% of rectum. When comparing the reference and delivered dose, there was no significant difference for Bladder D5cm3 for either technique. However, rectum in the high dose region benefited more from A-IMRT by being irradiated to a lower than reference dose in more fractions than 3DOF-VMAT. Hydrogel spacer reduced the rectal dose and was associated with a smaller deviation from reference dose for rectum D50% for A-IMRT. Despite the presence of large interfraction organ volumes changes, clinically acceptable dose was delivered to the prostate by both systems. A-IMRT facilitated a greater rectal sparing from the high dose region than 3DOF-VMAT. Further reduction in rectal dose could be achieved by hydrogel spacer to displace the rectum, or by adaptation delivered by VMAT.

CT-guided versus MR-guided radiotherapy: Impact on gastrointestinal sparing in adrenal stereotactic body radiotherapy

Background and purposeTo quantify the indication for adaptive, gated breath-hold (BH) MR-guided radiotherapy (MRgRTBH) versus BH or free-breathing (FB) CT-based image-guided radiotherapy (CT-IGRT) for the ablative treatment of adrenal malignancies. Materials and methodsTwenty adrenal patients underwent adaptive IMRT MRgRTBH to a median dose of 50 Gy/5 fractions. Each patient was replanned for VMAT CT-IGRTBH and CT-IGRTFB on a c-arm linac. Only CT-IGRTFB used an ITV, summed from GTVs of all phases of the 4DCT respiratory evaluation. All used the same 5 mm GTV/ITV to PTV expansion. Metrics evaluated included: target volume and coverage, conformality, mean ipsilateral kidney and 0.5 cc gastrointestinal organ-at-risk (OAR) doses (D0.5cc). Adaptive dose for MRgRTBH and predicted dose (i.e., initial plan re-calculated on anatomy of the day) was performed for CT-IGRTBH and MRgRTBH to assess frequency of OAR violations and coverage reductions for each fraction. ResultsThe more common VMAT CT-IGRTFB, with its significantly larger target volumes, proved inferior to MRgRTBH in mean PTV and ITV/GTV coverage, as well as small bowel D0.5cc. Conversely, VMAT CT-IGRTBH delivered a dosimetrically superior initial plan in terms of statistically significant (p ≤ 0.02) improvements in target coverage, conformality and D0.5cc to the large bowel, duodenum and mean ipsilateral kidney compared to IMRT MRgRTBH. However, non-adaptive CT-IGRTBH had a 71.8% frequency of predicted indications for adaptation and was 2.8 times more likely to experience a coverage reduction in PTV D95% than predicted for MRgRTBH. ConclusionBreath-hold VMAT radiotherapy provides superior target coverage and conformality over MRgRTBH, but the ability of MRgRTBH to safely provide ablative doses to adrenal lesions near mobile luminal OAR through adaptation and direct, real-time motion tracking is unmatched.

Verifying Plan QA for Online Adaptive Treatment in MR Linac

In addition to real-time tracking, a major advantage of the MR Linac is the ability to perform online plan adaptation in accordance with the patient anatomy of the day. This allows delivery of adequate tumor doses while ensuring surrounding organ at risk sparing. Treatment sites include pancreas prostate, lung and liver, among others. Typically, daily plan adaption leads to a change in monitor units (MU) from the original plan. This change can be over 100% at times. The vendor provides an online QA tool which is a secondary MU check. The purpose of this work is to evaluate the quality of plan QA in online adaptive IMRT treatments compared to physical, post-treatment measurements.We evaluated 32 online adapted plans (26 patients) which passed vendor-supplied secondary MU plan checks with a gamma criterion of 2mm/2%, and were treated clinically. We used both a diode array and an ion chamber for absolute dose measurement at isocenter. MU changes were evaluated in four groups: 0-25%, 26-50%, 51-75% and above 75% difference between adapted and original plans. Overall, MU changes ranged from 0%-102% between original and adapted fractions.The pass rates of the adapted plans were statistically significantly different from those of the original plans by up to 5% (2-tailed t-test). In 6 cases (19%) the relative dose passed and the absolute dose did not. In 4 cases (12%), the QA did not pass even using a 3mm/3% criteria. In 22 of 27 plans (82%) the ion chamber measurements were within 3% of the predicted dose. The other 5 plans had a larger than 3% difference between planned and measured dose at isocenter. In 5 plans the isocenter was too lateral to measure with an ion chamber.Our results show the vendor-supplied QA tool is in good correspondence with post treatment QA measurement. We did not find any correlation between the magnitude of MU changes between the original and adapted plans and the QA pass rates, which is reassuring given the large differences in some of the plans. Treatment site was not correlated to either the magnitude of MU changes or the QA passing rates. The vendor-supplied QA tool cannot be used when treating a patient with the original plan, and thus could not be assessed on these plans. As the optimization algorithm is identical in the treatment planning system and in the adaptive planning process in the treatment delivery computer, the underlying cause for the differences observed in passing rates is unclear. Overall, our results prove the reliability of the vendor-supplied MU secondary check as adequate real-time QA for confidently treating adapted plans.

Comparison of combinations of irradiation techniques and jaw conditions in intensity-modulated radiotherapy for lung cancer.

PurposeTo assist in the selection of a suitable combination of an irradiation technique and jaw condition in intensity‐modulated radiotherapy (IMRT) and volumetric‐modulated arc radiotherapy (VMAT) for lung cancer treatment plans.Materials and methodsThirty patients with lung cancer who underwent radiotherapy were enrolled retrospectively. They were categorized as having central lung cancer, peripheral lung cancer with mediastinal lymph node metastasis (peripheral E lung cancer), and peripheral lung cancer without mediastinal lymph node metastasis (peripheral N lung cancer). Four treatment plans were designed for each patient: fixed jaw and adaptive jaw IMRT technique (FJ‐IMRT and JA‐IMRT), and fixed jaw and jaw tracking VMAT technique (FJ‐VMAT and JT‐VMAT). The dose parameters of the four group plans were compared and analyzed.ResultsCompared to FJ‐IMRT, JA‐IMRT significantly reduced the mean dose (Dmean) and volume percentage of 5 Gy (V5Gy) of the total lung in central and peripheral N lung cancer. Similarly, compared to FJ‐VMAT, JT‐VMAT provided better protection to most organs at risk (OARs), particularly for total lung and heart. In comparison with IMRT, VMAT significantly improved the conformity index (CI) of the planning target volume for the three lung cancer classifications, and it reduced the dose of almost all OARs except V5Gy and Dmean of the total lung. Moreover, the mean monitor units of the VMAT groups were far lower than the IMRT groups.ConclusionBased on the dosimetric findings and considering clinical data published on lung and heart side effects, we propose recommendations on the preferred treatment technique based on tumor location and pulmonary function. For central lung cancer with normal pulmonary function, we advise JT‐VMAT techniques. Conversely, for central lung cancer with poor pulmonary function, we recommend JA‐IMRT techniques. We advocate JA‐IMRT for peripheral E lung cancer. For peripheral N lung cancer, JT‐VMAT techniques are strongly recommended.

A Study to Assess the Dosimetric Impact of the Anatomical Changes Occurring in the Parotid Glands and Tumour Volume during Intensity Modulated Radiotherapy using Simultaneous Integrated Boost (IMRT-SIB) in Head and Neck Squamous Cell Cancers.

BackgroundAnatomical variations in head and neck cancer during IMRT leads to volume shrinkage, results in dosimetric variations in tumour and normal tissue including parotid glands, with a risk of radiation toxicities.Methods30 patients with a stage II–IV head and neck squamous cell carcinoma (HNSCC) were treated with definitive IMRT‐SIB and concomitant chemotherapy. Volumetric and dosimetric variations were evaluated during the period of IMRT by recalculating and obtaining dose‐volume histograms of re‐contoured target volumes and parotid glands on repeat CT scans taken multiple times during treatment (CT1, CT2, CT3 and CT4).ResultsResult showed significant (p < 0.001) mean decrease in both primary and nodal tumors volume with time whereas increase (p < 0.01 or p < 0.001) in respective V100 (%) and D2% (Gy). The mean parotid gland dose increased (p < 0.01 or p < 0.001) with time, whereas parotid gland volume and distance between plan isocenter and centre of mass of parotid glands decreased (p < 0.05 or p < 0.001) with time. Patient's mean weight and neck circumference both decrease (p < 0.001) with time whereas ECOG score increase (p < 0.001) with time. The mucosal toxicity increased significantly (p < 0.001) with time. The change in both weight and neck circumference showed significant (p < 0.001) and direct (positive correlation) association with change in parotid gland volume.ConclusionIf the PTV and normal anatomy are changing with time, adaptive IMRT would be beneficial radiation dose delivery where possible.

P82.04 Adaptive Radiation Therapy with Consolidation Sintilimab in Stage III NSCLC: Challenges in Recruiting Patients for Adjuvant Immunotherapy

The PACIFIC reported a significantly improved overall survival for consolidative durvalumab after chemoradiotherapy in unresectable stage III non-small cell lung cancer (NSCLC) in 2018. However, the details in the exclusion of patient enrollment were not reported. It is unclear what proportion of patients after chemoradiotherapy would be eligible to receive immunotherapy. In this study, we aimed to recruit all for consolidation sintilimab, an anti-PD-1 antibody, after definitive chemoradiotherapy using adaptive radiotherapy which can target to the shrunk tumor to reduce the dose to surrounding normal tissues and decrease the toxicities. This was a single-arm prospective phase II trial (CARTAI; NCT03732430). Patients with histologically confirmed NSCLC, unresectable stage III medically fit for concurrent chemoradiotherapy were eligible. Radiation therapy was delivered using mid-treatment CT guided adaptive IMRT. Sintilimab was given within 45 days after completion of RT, when patients had grade 1 or less acute toxicity, with ECOG PS 0 or 1, adequate hematologic, liver and kidney function. Any patients who had unresolved grade 2 or higher toxicity were excluded from enrollment. The prescription doses of radiotherapy were 64-66Gy to the GTV and 54Gy to the PTV in 30 fractions, unless exceeding the dose constraints. The patents were intravenously given sintilimab, an anti-PD-1 antibody, 200mg q3w. We initially screened potential patients before the radiotherapy and all interested patients were treated consistently with adaptive RT. Final written consent was obtained, and eligibility was confirmed after completion of radiotherapy. From November 2018 to December 2019, after the initial screening, 107 consecutive patients potentially eligible received concurrent chemoradiation received adaptive IMRT. Eight-eight patients failed for enrollment of consolidation sintilimab. In which, seventy (80%) patients refused to participate the study at the last minutes. Eighteen of 88 (20%) did not meet the inclusion criteria after the end of radiotherapy. main ineligible reasons were grade 2 or higher toxicities, including radiation-induced pneumonitis in 7 patients, unresolved esophagitis in 5, 2 developed both, and 2 with unresolved leukopenia. A total of 19 patients (17.8%) consented to participate in the adjuvant immunotherapy. Four of them (21.5%) were found ineligible, including 2 patients with grade 2 radiation pneumonitis, 1 with esophagitis, and 1 with leukopenia. There were finally 15 patients (78.9%) enrolled in this study. This study found approximately twenty percent of all consented and refused patients were ineligible to receive consolidative immunotherapy after the end of concurrent chemoradiotherapy. The main barrier for eligibility was the radiation-induced acute toxicities, especially pneumonitis and esophagitis.

Adaptive intensity-modulated radiotherapy with simultaneous integrated boost for stage III non-small cell lung cancer: Is a routine adaptation beneficial?

PurposeTumor and anatomical changes during radiotherapy have been observed in stage III non-small cell lung cancer (NSCLC) from many previous studies. We hypothesized that a routinely scheduled adaptive radiotherapy would have clinical important dose benefits to lower the risk of toxicities, without increasing the tumor recurrences. MethodsWe retrospectively reviewed 92 consecutive patients with inoperable stage III NSCLC between November 2017 and March 2019. All eligible patients should received simultaneously integrated boost (SIB) using intensity-modulated radiation therapy (IMRT). A mid-treatment CT simulation and a new adapted plan were routinely given after the first 20 fractions. The organs at risk (OARs) were delineated per RTOG 1106 atlas. Dose-volume histograms were quantitatively compared between the initial and composite adaptive plans. Logistic regression was applied to analyze the dose–response relationship. Clinical endpoints included acute symptomatic radiation pneumonitis (RP2) and esophagitis (RE2), local and regional tumor control, and progression-free survival (PFS). ResultsSixty-four eligible patients received adaptive SIB-IMRT were consecutively included. The GTVs reduced by a median of −38.2% after 42 to 44 Gy in 20 fractions of radiotherapy. By adapting to tumor and anatomical changes, dosimetric parameters of OARs decreased significantly. The mean lung dose decreased by an average of −74.8 cGy, and mean esophagus dose was lower by 183.1 cGy. We found grade 2 or higher acute RP in 11 patients (17.2%), and RE2 in 28 patients (43.8%). Commonly used lung and esophagus dose metrics were significantly associated with RP2 and RE2. The adaptation could reduce RP2 probability by 3%, and RE2 risk by 5%. Subgroups with higher OARs dose or larger tumor shrinkage may get more dose and toxicities benefits. The estimated median PFS was 12.5 months from the start of radiotherapy. ConclusionsWe demonstrated that the routinely adaptive SIB-IMRT strategy could significantly reduce the dose to surrounding normal tissues, potentially lower the associated acute RP and RE, without increasing the risk of tumor recurrences.

Adaptive intensity-modulated radiotherapy in head and neck cancer patients treated by chemoradiotherapy: To quantify temporal changes during the course of radiotherapy and to study the impact of these changes on the baseline treatment plans

Aims: The purpose of study was to evaluate the volumetric changes and dose perturbations, occurring in various target volumes and organs at risk during radiotherapy. Materials and Methods: Ten locally advanced head and neck cancer patients were recruited. The rate of volume change and dose perturbations for targets and organs at risk was calculated by superimposing repeatradiation treatment planning scans (RTPs) over baseline RTP-computerized tomography. Results: The mean volume regression for primary target was 19% (0–48.5) for first (repeat) RTP scan and 29.4% (4.5–52.8) for second (repeat) RTP scan; for nodal target, mean volume regression was 33.4% (3.4–67.2) and 52.9% (36.5–78.7), respectively; for the left parotid, mean volume regression was 24.4% (13.5–40.8) and 33.6% (9.4–52.4), respectively, and for right parotid, mean volume regression was 24.13% (9.4–52.4) and 35.55% (16–52), respectively. For the left parotid, mean displacement was 0.21 cm (0–0.5) for first repeat RTP and 0.28 cm (0–0.6) for second repeat RTP while for right parotid it was 0.26 cm (0–0.8) and 0.36 cm (0.1–1.0), respectively. These all movements for both parotids were in medial directions. Only one patient had crossed Dmax cord beyond 50 Gy, i.e., 54.07 Gy. For left parotid gland, mean dose was increased up to 26.7% (2–26.7) and 33% (2–33); right parotid, mean dose was increased up to 35% (1.6–35) and 48.9 (2–48.9), respectively. Conclusion: As a consequence of regression in tumor and parotid glands volumes resulted in dose perturbation of target volumes up to 21%. Similarly, parotid glands received up to 49% excess of planned dose, due to its medial migration.

P1.18-15 Dosimetric and Toxicity Benefits of Adaptive IMRT in Patients with Stage III Non-Small Cell Lung Cancer

Multiple studies observed anatomical changes or tumor shrinkage during concurrent chemoradiotherapy in patients with non-small cell lung cancer (NSCLC). Mid-treatment CT based adaptive radiotherapy targeting to the shrunken tumor can reduce the dose to adjacent normal tissue or potentially deliver a higher dose to the tumor. We aimed to quantitatively analyze the benefit of intensity-modulated radiotherapy (IMRT) adapting to CT changes at the 20th fraction in stage III NSCLC patients. We retrospectively evaluated consecutive patients with unresectable stage III NSCLC treated with adaptive IMRT from November 2017 to August 2018. The eligibility criteria included a mid-treatment CT simulation for replanning at the 20th fraction and a follow-up of at least 6 months. The prescribed dose was 64-66 Gy in 30 fractions unless exceeding the dose limit. Normal tissues were delineated according to RTOG1106 atlas on organs at risk under the supervision of a senior physician. Dose-volume histograms were calculated for the initial plans, composite adaptive plans, and lung isotoxic boost plans. Radiation pneumonitis (RP) and esophagitis (RE) were graded per CTCAE v4.03. Univariate logistic regression was applied to analyze the correlation between dosimetric factors and adverse events. 53 patients were eligible in this study. The average GTV shrinkage was -40.9% at the 20th fraction. Comparing the dosimetric factors of the composite adaptive plans to the initial ones, the GTV coverage was found marginally higher (P=0.002). The doses to normal tissues were significantly lower (all Ps<0.001) in heart mean dose by 109.5 cGy, esophagus V60 by 1.53%, cord maximum dose by -272.7 cGy, lung V20 and mean lung dose (MLD) by 1.11% and 79.2 cGy, respectively. The tumor targets could potentially get an average lung isotoxic boost of 481 cGy. Eight patients (15.1%) had grade 2 RP while no grade 3 or higher RP occurred. Twenty-three patients (43.4%) developed grade ≥ 2 RE. MLD was significantly associated with grade 2 RP with an odds ratio of 1.39 per 100 cGy increase (95% CI, 1.01 to 1.91; P=0.042). Esophagus V60 was significantly associated with grade ≥ 2 RE with an odds ratio of 1.15 per 1% increase (95% CI, 1.04 to 1.28; P=0.009). (Table 1)Tabled 1FactorsInitial PlansAdaptive PlansMean difference95%CIP ValueTargetsPGTV (%)92.9693.810.850.331.370.002PTV(%)94.1394.540.410.350.800.033LungV5(%)46.7745.72-1.05-0.70-1.41<0.001V20(%)25.1524.04-1.11-0.80-1.42<0.001V30(%)18.6217.60-1.02-0.77-1.27<0.001MLD (cGy)1411.41332.2-79.2-60.1-98.4<0.001HeartV30(%)17.4015.11-2.29-0.94-3.620.001V40(%)10.879.06-1.81-0.98-2.64<0.001V55(%)4.062.79-1.27-0.76-1.77<0.001Mean Dose(cGy)1504.51395.0-109.5-67.88-151.22<0.001PericardiumV30(%)32.1730.43-1.74-0.77-2.700.001V40(%)25.7024.00-1.7-0.76-2.640.001V55(%)13.8711.87-2-1.34-2.66<0.001Mean Dose(cGy)2192.92091.2-101.7-60.00-143.3<0.001EsophagusV40(%)39.4336.49-2.94-1.62-4.27<0.001V50(%)27.8924.08-3.81-2.36-5.27<0.001V60(%)7.576.04-1.53-0.96-2.09<0.001Max Dose(cGy)6498.36336.7-161.6-101.99-221.3<0.001CordMax Dose(cGy)4113.03840.3-272.7-209.51-335.93<0.001 Open table in a new tab By adapting to the changes on CT scans at the 20th fraction, the adaptive IMRT approach provides significant dosimetric benefits and has the potential to lower the risk of symptomatic pneumonitis and esophagitis in stage III NSCLC.

Impact of adaptive intensity-modulated radiotherapy on the neutrophil-to-lymphocyte ratio in patients with nasopharyngeal carcinoma

PurposeNutritional status and haematological parameters are related to the prognosis of patients treated with radiotherapy, but the correlation between adaptive radiotherapy (ART) and haematological indicators has never been reported. This study explores the influence of ART on the change in haematological indicators and provides a theoretical basis for the use of ART in patients with nasopharyngeal carcinoma (NPC).Patients and methodsWe retrospectively analysed 122 patients with NPC from January 2014 to December 2015. Patients in two treatment groups were matched using the propensity score matching method at a ratio of 1:1. The data were analysed with the Kaplan–Meier method, log-rank tests, regression analyses and paired t tests.ResultsSignificant differences were detected for changes in the neutrophil-to-lymphocyte ratio (ΔNLR), circulating lymphocyte count (ΔCLC), circulating platelet count (ΔCPC), and circulating neutrophil granulocyte count (ΔCNC) during radiotherapy (P = 0.002, P < 0.001, and P = 0.036, respectively) between the ART and non-ART groups. Differences in acute radiation injury to the parotid glands (PGs) (P < 0.001), skin (P < 0.001), and oral structures (P < 0.001), Δweight (kg) (P = 0.025), and Δweight (%) (P = 0.030) were also significant between the two groups. According to univariate and multivariate analyses, ART (R = 0.531, P = 0.004), skin-related side effects (R = 0.328, P = 0.020), and clinical stage (R = -0.689, P < 0.001) are influencing factors for the ΔNLR in patients. ART is also the influencing factor for the ΔCLC (R = 2.108, P < 0.001) and the only factor affecting the ΔCPC (R = 0.121, P = 0.035). Based on subgroup analyses, for stage T1–2N0–3 disease, ΔCLC was higher in patients in the ART group than in patients in the non-ART group (P < 0.001, P = 0.003, and P = 0.003).ConclusionART ameliorates changes in haematological indexes (ΔNLR, ΔCLC, and ΔCPC) and reduces side effects to the skin and PGs and weight loss during radiotherapy in patients with NPC, and patients with stage T1–2 disease experience a greater benefit.

EP-1580 Adjuvant radiotherapy in prostate cancer patients–bRFS and toxicity using adaptive IMRT technique

EP-1580 Adjuvant radiotherapy in prostate cancer patients–bRFS and toxicity using adaptive IMRT technique