Dose Reduction Of Radiotherapy Research Articles

Radiotherapy dose de-escalation in patients with high grade non-Hodgkin lymphoma in a real-world clinical practice.

The standard treatment of non-Hodgkin lymphoma (NHL) comprises combined modality treatment, radiotherapy (RT), and chemotherapy with rituximab which has significantly improved both disease-free survival (DFS) and overall survival (OS). However, there is no uniformity in radiation dose usage in these patients. In this retrospective study, we compared lower radiation dose with higher in patients with aggressive NHL. From 2007 to 2017, treatment records of all high-grade NHL or diffuse large B-cell lymphoma and non-central nervous system NHL were included. We compared response rates, OS and DFS of patients who received ≤30 Gy RT to those with >30 Gy. Univariate and multivariate analyses were done to determine factors affecting prognosis, i.e., age, sex, stage, International Prognostic Index (IPI), adding rituximab, and radiation dose. A total of 184 NHL patients treated with combined modality or radiation alone having complete follow-up details were analyzed. At median follow-up of 66.8 months, 5-year OS was 72.8% in high-dose group versus 69.9% in low-dose group (p = 0.772) and 5-year DFS 64.7% versus 64.1% (p = 0.871). Patients having early-stage disease receiving low dose and those with advanced disease treated with >30 Gy had better OS and DFS though not statistically significant. Adding rituximab was associated with significantly better OS and DFS irrespective of radiation dose delivered. High IPI score and omitting rituximab were the only factors that significantly worsened both OS and DFS. Acute radiation toxicities were comparable in both groups (p = 0.82). Among late toxicities, no patient developed a second malignancy and 5% died due to cardiovascular complications (p = 0.595) though only two patients (1.1%) had received thoracic radiation. The two groups had comparable response rates, acute toxicities, DFS and OS. This study suggests that RT dose reduction may be possible in high-grade NHL without compromising the DFS and OS.

Current Evidence of a Deintensification Strategy for Patients with HPV-Related Oropharyngeal Cancer.

Simple SummaryHuman papillomavirus (HPV)-related oropharyngeal cancer represents a distinct disease entity, showing favorable treatment responses and survival outcomes. While the deintensification of treatment for HPV-related oropharyngeal cancer is widely considered necessary, details concerning patient selection and optimal strategies are undetermined. The heterogeneity of study populations and interventions in trials complicate the ability of physicians to apply the results in daily practice. The evolving landscape also requires physicians to consistently update the results of these trials. This article reviews the most recent evidence on the deintensification of HPV-related oropharyngeal cancer. We aim to provide physicians with some guidance regarding management options and assist researchers in appropriately designing trials in the future.Human papillomavirus (HPV)-related oropharyngeal cancer differs from HPV-negative oropharyngeal cancer in terms of etiology, epidemiology, and prognosis. Younger and lower comorbidity patient demographics and favorable prognosis allow HPV-related oropharyngeal cancer patients to anticipate longer life expectancy. Reducing long-term toxicities has become an increasingly important issue. Treatment deintensification to reduce toxicities has been investigated in terms of many aspects, and the reduction of radiotherapy (RT) dose in definitive treatment, replacement of platinum-based chemotherapy with cetuximab, response-tailored dose prescription after induction chemotherapy, and reduction of adjuvant RT dose after transoral surgery have been evaluated. We performed a literature review of prospective trials of deintensification for HPV-related oropharyngeal cancer. In phase II trials, reduction of RT dose in definitive treatment showed comparable survival outcomes to historical results. Two phase III randomized trials reported inferior survival outcomes for cetuximab-based chemoradiation compared with cisplatin-based chemoradiation. In a randomized phase III trial investigating adjuvant RT, deintensified RT showed noninferior survival outcomes in patients without extranodal extension but worse survival in patients with extranodal extension. Optimal RT dosage and patient selection require confirmation in future studies. Although many phase II trials have reported promising outcomes, the results of phase III trials are needed to change the standard treatment. Since high-level evidence has not been established, current deintensification should only be performed as part of a clinical study with caution. Implementation in clinical practice should not be undertaken until evidence from phase III randomized trials is available.

Efficacy of Kanglaite against radiotherapy-induced mucositis in head and neck cancer, a phase II trial

PurposeTo explore the potential protective effect of Kanglaite injection against radiotherapy-induced mucositis in patients with head and neck cancer. Patients and methodsThis was an open-label, single-arm, and phase II trial. The primary endpoint was the incidence of grade 3–4 radiation-induced mucositis. The secondary endpoints were hematological toxicity, non-hematological toxicity, nutritional status, and quality of life. All patients received 20g Kanglaite daily concurrently with radiotherapy. ResultsThe data of 46 patients were available for analysis. The incidence rates of grade 3 mucositis, pain, dysphagia, and neutropenia were 10.9%, 2.2%, 10.9%, and 6.5%, respectively, while the incidence of grade 4 acute toxicities was zero. The rate of opioid use was 2.2%. Radiotherapy dose reduction was 2.2% and no irradiation field was modified. The nutritional supports were oro-enteral nutritional supplements (13.0%), TPN (10.9%), and feeding tubes (0%) during radiotherapy. After radiotherapy, 52.2% of patients lost weight, and the weight loss was <10%. The mean pain score in the QLQ-H&N35 and QLQ-C30 was <50. Patients had nearly normal physical, emotional, and cognitive functions. ConclusionsA low incidence of grade 3–4 radiation-induced mucositis and no severe acute toxic events, with favorable nutritional status and quality of life, were observed in cancer patients after Kanglaite injection. Our findings highlight the need for a prospective, multicenter, and randomized study to investigate the effect of Kanglaite injection on the reduction of radiation-induced mucositis in patients with head and neck cancer.

Evaluation of Substantial Reduction in Elective Radiotherapy Dose and Field in Patients With Human Papillomavirus–Associated Oropharyngeal Carcinoma Treated With Definitive Chemoradiotherapy

Several de-escalation strategies for human papillomavirus (HPV)-associated oropharyngeal carcinoma (OPC) have focused on deintensifying gross disease treatment. Reduction of radiotherapy dose and target volume to subclinical regions may achieve good clinical outcomes with favorable patient quality of life (QOL). To determine outcomes from a systematic approach of reducing radiotherapy dose and target volume to the elective treatment regions in patients with HPV-associated OPC undergoing concurrent chemoradiotherapy (CCRT). This retrospective cohort study included 276 consecutive patients with HPV-positive OPC receiving CCRT from March 1, 2017, to July 31, 2019. Data were analyzed from February 23 to September 13, 2021. Elective nodal and subclinical regions received 30 Gy of radiotherapy in 15 fractions, followed by a cone down of 40 Gy in 20 fractions to gross disease for a total dose of 70 Gy. The high retropharyngeal nodal basins in the node-negative neck and bilateral levels IB and V basins were omitted. Patients were followed up to evaluate locoregional control as the primary outcome and distant metastasis-free survival, progression-free survival, and overall survival as secondary outcomes. Quality-of-life data were obtained at each visit when feasible. Among the 276 patients included in the analysis, the median age was 61 (range, 36-87) years; 247 (89.5%) were men; and 183 (66.3%) had less than 10 pack-years of smoking history. Most patients (251 [90.9%]) were White. Overall, 87 (31.5%) had cT3-cT4 disease and 65 (23.5%) had cN2-cN3 disease per the 8th edition of the American Joint Committee on Cancer Staging Manual. One hundred seventy-two patients (62.3%) completed 300-mg/m2 high-dose cisplatin therapy. During a median follow-up of 26 (range, 21-32) months, 8 patients developed locoregional recurrence, including 7 at the primary site or gross nodes that received a total dose of 70 Gy and 1 with a persistent node not previously identified as gross disease that received a total dose of only 30 Gy. The 24-month locoregional control was 97.0%; progression-free survival, 88.0%; distant metastasis-free survival, 95.2%; and overall survival, 95.1%. During treatment, 17 patients (6.2%) required a feeding tube. At 24 months, most of the QOL composite scores (jaw-related problems, pain, social contact, eating, speech, and swallow) were comparable or superior to baseline measures except for senses, dry mouth, muscular tension, and cognitive functioning, which improved over time but remained marginally worse than baseline. This cohort study found that the evaluated de-escalation strategy for elective regions showed favorable clinical outcomes and QOL profiles. Long-term follow-up data will help affirm the efficacy of this strategy as a care option for treating HPV-associated OPC with primary CCRT.

De-Escalation Strategies of (Chemo)Radiation for Head-and-Neck Squamous Cell Cancers-HPV and Beyond.

Simple SummaryHPV-related oropharyngeal squamous cell carcinoma patients have a very good prognosis but are often suffering from long-term treatment-induced toxicities. Therefore, a plethora of de-escalation trials is examining whether treatment for HPV-induced oropharyngeal carcinoma can be de-escalated without compromising the favorable outcomes. The purpose of this review was to present and critically discuss the published as well as the ongoing de-escalation trials in head-and-neck squamous cell carcinoma, in particular for HPV-related oropharyngeal carcinoma. De-escalation studies are using several approaches such as radiotherapy dose reduction, target volume reduction, omission of concomitant chemotherapy, replacement of cisplatin through less toxic systemic agents, omission of adjuvant (chemo)radiation after primary surgery and selection of suitable patients by induction chemotherapy or peritherapeutic hypoxia imaging. Although many promising results have been obtained from several Phase I and II trials, the two Phase III de-escalation trials failed to show the equivalence of the de-escalated treatment arm, so that so far, no treatment de-escalation can be recommended outside of clinical trials.Oncological outcomes for head-and-neck squamous cell carcinoma (HNSCC) patients are still unsatisfactory, especially for advanced tumor stages. Besides the moderate survival rates, the prevalence of severe treatment-induced normal tissue toxicities is high after multimodal cancer treatments, both causing significant morbidity and decreasing quality of life of surviving patients. Therefore, risk-adapted and individualized treatment approaches are urgently needed for HNSCC patients to optimize the therapeutic gain. It has been a well-known fact that especially HPV-positive oropharyngeal squamous cell carcinoma (OSCC) patients exhibit an excellent prognosis and may therefore be subject to overtreatment, resulting in long-term treatment-related toxicities. Regarding the superior prognosis of HPV-positive OSCC patients, treatment de-escalation strategies are currently investigated in several clinical trials, and HPV-positive OSCC may potentially serve as a model for treatment de-escalation also for other types of HNSCC. We performed a literature search for both published and ongoing clinical trials and critically discussed the presented concepts and results. Radiotherapy dose or volume reduction, omission or modification of concomitant chemotherapy, and usage of induction chemotherapy are common treatment de-escalation strategies that are pursued in clinical trials for biologically selected subgroups of HNSCC patients. While promising data have been reported from various Phase II trials, evidence from Phase III de-escalation trials is either lacking or has failed to demonstrate comparable outcomes for de-escalated treatments. Therefore, further data and a refinement of biological HNSCC stratification are required before deescalated radiation treatments can be recommended outside of clinical trials.

Randomized Clinical Trial on Reduction of Radiotherapy Dose to the Elective Neck in Head and Neck Squamous Cell Carcinoma: Results on the Quality of Life.

A randomized trial was initiated to investigate whether a reduction of the dose to the elective nodal sites would result in less toxicity and improvement in Quality of Life (QoL) without compromising tumor control. This paper aimed to compare QoL in both treatment arms. Two-hundred head and neck cancer patients treated with radiotherapy (RT) or chemo-RT were randomized (all stages, mean age: 60years, M/F: 82%/18%). The elective nodal volumes of patients randomized in the experimental arm were treated up to a 40Gy equivalent dose. In the standard arm, the elective nodal volumes were treated up to a 50Gy equivalent dose. The QoL data were collected using The European Organization for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 and the EORTC Head and Neck Cancer module (H&N35). A trend toward less decline in QoL during treatment was observed in the 40Gy arm compared to the 50Gy arm. Statistically significant differences for global health status, physical functioning, emotional functioning, speech problems, and trouble with social eating in favor of the 40Gy arm were observed. A clinically relevant better outcome in the 40Gy arm was found for physical functioning at the end of therapy. QoL during RT for head and neck cancer tends to be less impaired in the 40Gy arm. However, reducing the dose only on the elective neck does not result in clinically relevant improvement of QoL. Therefore, additional treatment strategies must be examined to further improve the QoL of HNSCC patients.

Radiation Dose Reduction in Early-Stage Hodgkin Lymphoma

IntroductionTreatment for early-stage Hodgkin lymphoma (HL) involves radiotherapy (RT), chemotherapy, or combined modality therapy (CMT). We analyzed reduction of RT dose in CMT, particularly in the context of German Hodgkin Study Group (GHSG) HD10 randomized trial results of 2010. Patients and MethodsThe National Cancer Data Base was queried for patients with stage I-II HL receiving CMT. RT dose and associated characteristics were analyzed. Stage I and absence of B symptoms were used as a surrogate for early-stage favorable disease. ResultsOf 31,301 patients with stage I-II HL, 11,457 received CMT between 2004 and 2015. Using the surrogate defined above, 1955 patients (17.1%) were classified as having favorable disease. The majority (61.6%) received 30-36 Gy, while 7.0% received 20 Gy. The provision of 20 Gy was more common in stage I patients (12.3% vs. 5.4% in stage II) and at academic facilities (10.8% vs. 6.3%-8.9% at other facilities). Use of 20 Gy (vs. 30-36 Gy) was less likely with thorax site (odds ratio [OR] 0.43 vs. head and neck), stage II disease (OR 0.41), and B symptoms (OR 0.33). Notably, the use of 20 Gy increased dramatically after 2010 (the year of publication of GHSG HD10 trial results), with rates of 12.3% in 2010-2015 versus 0.1% in 2004-2009 (OR 6.3, P < .001). This was even more pronounced in cases of favorable early-stage disease, with 25.5% after 2010 versus 2.8% before 2010 (OR 13.2, P < .001). The use of doses > 36 Gy decreased over a corresponding time period (OR 0.44, P < .001). ConclusionAnalysis of CMT for patients with early-stage HL demonstrates variability in RT dose, including increasing use of 20 Gy and decreasing use of high doses > 36 Gy.

Decrease in treatment intensity predicts worse outcome in patients with locally advanced head and neck squamous cell carcinoma undergoing radiochemotherapy

PurposeRadiochemotherapy (RCT) is an effective standard therapy for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Nonetheless, toxicity is common, with patients often requiring dose modifications.MethodsTo investigate associations of RCT toxicities according to CTCAE version 5.0 and subsequent therapy modifications with short- and long-term treatment outcomes, we studied all 193 patients with HNSCC who received RCT (70 Gy + platinum agent) at an academic center between 03/2010 and 04/2018.ResultsDuring RCT, 77 (41%, 95% CI 34–49) patients developed at least one ≥ grade 3 toxicity, including seven grade 4 and 3 fatal grade 5 toxicities. The most frequent any-grade toxicities were xerostomia (n = 187), stomatitis (n = 181), dermatitis (n = 174), and leucopenia (n = 98). Eleven patients (6%) had their radiotherapy schedule modified (mean radiotherapy dose reduction = 12 Gy), and 120 patients (64%) had chemotherapy modifications (permanent discontinuation: n = 67, pause: n = 34, dose reduction: n = 7, change to other chemotherapy: n = 10). Objective response rates to RCT were 55% and 88% in patients with and without radiotherapy modifications (p = 0.003), and 84% and 88% in patients with and without chemotherapy modifications (p = 0.468), respectively. Five-year progression-free survival estimates were 20% and 50% in patients with and without radiotherapy modifications (p = < 0.001), and 53% and 40% in patients with and without chemotherapy modifications (p = 0.88), respectively.ConclusionsReductions of radiotherapy dose were associated with impaired long-term outcomes, whereas reductions in chemotherapy intensity were not. This suggests that toxicities during RCT should be primarily managed by modifying chemotherapy rather than radiotherapy.

Randomized clinical trial on reduction of radiotherapy dose to the elective neck in head and neck squamous cell carcinoma; update of the long-term tumor outcome

Background and purposeA multicenter prospective randomized controlled trial was performed to investigate whether dose reduction to the elective nodal volume (PTVelect) in head and neck carcinoma reduces radiation-induced dysphagia, primary endpoint, without compromising tumor control, secondary endpoint. Here, we report on the long-term follow-up of the secondary endpoint (NCT01812486). Materials and methodsTwo hundred patients treated with primary (chemo)radiotherapy (RT) were randomized (1:1) between the standard arm, irradiation to PTVelect up to an equivalent dose (EQD2) of 50 Gy and the experimental arm, irradiation to PTVelect up to EQD2 of 40 Gy. The primary tumor and involved nodes were treated according to the standard of care, EQD2 70 Gy (PTVhigh). Regional recurrences (RR) were projected on the initial RT planning-CT to identify the recurrence localization. ResultsThe 5-year (5Y) RR was 14.0% (CI95% 7.9; 21.8) in the 40 Gy arm versus 7.5% (CI95% 3.3; 14.0) in the 50 Gy arm (p = 0.10). Majority of RR in the 40 Gy arm (9/13) were projected in PTVhigh and 2 RR were seen outside the treated RT volume. Only 2 RR occurred in PTVelect irradiated up to 40 Gy which was the same number as RR occurring in the 50 Gy PTVelect.The 5Y-overall survival (OS) was 56.5% (CI95% 45.7; 65.9) in the 40 Gy arm versus 49.6% (CI95% 39.0; 59.2) in the 50 Gy arm (p = 0.56). ConclusionAt 5-years, no statistically significant differences regarding OS, local recurrence, RR nor distant metastases were observed between both treatment arms. This study is underpowered to undoubtedly demonstrate non-inferiority. However, since in both arms only two RR in the PTVelect were observed, reducing the dose to PTVelect appears safe and should be further investigated.

Reduction of Radiotherapy Dose to the Elective Neck in Head and Neck Squamous Cell Carcinoma; Update of the Long-Term Tumor Control of a Randomized Clinical Trial

A multicenter prospective randomized controlled trial was performed to investigate whether dose reduction to the elective nodal volume (PTVelect) in head and neck squamous cell carcinoma (HNSCC) reduces radiation-induced dysphagia, primary endpoint, without compromising tumor control, secondary endpoint. In this abstract, we report on the long-term follow-up of the secondary endpoint. Patients with non-metastatic HNSCC were treated with primary (chemo)radiotherapy (RT) including irradiation of the bilateral elective neck. Patients were randomized (1:1) between the standard arm, irradiation to PTVelect up to an equivalent dose of 50 Gy and the experimental arm, irradiation to PTVelect up to an equivalent dose of 40 Gy. The primary tumor and involved nodes were treated according to the standard of care up to an equivalent dose of 70 Gy (PTV high dose). (NCT01812486) Secondary endpoints were overall survival (OS), local recurrence (LR), regional recurrence (RR) and distant metastasis (DM). OS was estimated using Kaplan-Meier method and compared with log-rank test. LR, RR and DM were assessed using competing risk method and compared with Pepe and Mori’s test. RR were projected on the initial RT planning computed tomography studies to identify the localization of recurrence. Between 2008 and 2011, 200 patients were enrolled. Median follow up was 7.6 years (IQR 6.6-8.7). The 5 year (5Y) OS was 56.5% (CI95% 45.7;65.9) in the 40 Gy arm versus 49.6% (CI95% 39.0;59.2) in the 50 Gy arm (p=0.56). In the reduced 40 Gy arm, 5Y-LR was 17.2% (CI95% 10.4;25.4) versus 13.8% (CI95% 7.7;21.5) in the standard 50 Gy arm (p=0.39); 5Y-RR was 14.0% (CI95% 7.9;21.8) versus 7.5% (CI95% 3.3;14.0) (p=0.10) and 5Y-DM rate was 12.9% (CI95% 7.1;20.6) versus 24.4% (CI95% 16.3;33.5), respectively (p=0.07). Majority of RR in the 40 Gy arm (9 of 13) were projected in the PTV high dose and 2 RR were seen outside the treated RT volume (Table 1). Only 2 RR occurred in PTVelect irradiated up to 40 Gy which was the same number as RR occurring in the 50 Gy PTVelect. At 5 years of follow-up, no statistically significant differences regarding OS, LR, RR nor DM were observed between both treatment arms. This study is underpowered to undoubtedly demonstrate non-inferiority and to change the standard of care to 40 Gy. However, since only two RR in the PTVelect in both treatment arms were observed, reducing the dose to PTVelect appears safe and these results support further research in de-escalating the dose to the elective neck.Abstract 31; Table 1Regional recurrences classified according to the treatment arm (LRR: Locoregional recurrence; IRR: Isolated regional recurrence)40 Gy50 GyRecurrence n=13Recurrence n=7PTV high dose9IRR5PTV high dose5IRR1LRR2LRR1RR + DM2LRR + DM1RR + DM2PTV elect2IRR1PTV elect2IRR1RR + DM1LRR + DM1Outside planning volume2LRR2 Open table in a new tab

Is a reduction of radiation dose feasible in patients affected by glioblastoma undergoing radio-chemotherapy according to MGMT promoter methylation status without jeopardizing survival?

ObjectiveTo explore therapeutic results of different radiotherapy (RT) dose schedules combined to Temozolomide (TMZ)-RT treatment in newly diagnosed glioblastoma (GB), according to the O (6)-methylguanine-DNA methyltransferase (MGMT) methylation status. Patients and methodsPatients with newly diagnosed GB received either standard (60-59.4 Gy) or reduced (54-52 Gy) dose radiation therapy (RT) with concurrent and adjuvant TMZ between June 2010 and October 2016. We retrospectively evaluated the therapeutic effectiveness of the RT ranges schedules in terms of overall survival (OS) with univariate and multivariate analysis, after analyzing the MGMT methylation status. ResultsOne hundred and seventeen patients were selected for the present analysis out of 146 total treated patients accrued. Seventy-two out of the selected cases received the standard RT-TMZ course (SDRT-TMZ) whereas the remaining 45 underwent the reduced dose schedule (RDRT-TMZ). The analysis according to the MGMT promoter methylation status showed that, in methylated-MGMT GB patients, SDRT-TMZ and RDRT-TMZ groups did not show different median OS (p = ns) according to the two RT schedules, independently by the extent of surgical resection. Instead, a difference in survival outcomes was confirmed in unmethylated-MGMT GB patients with better survival for patients undergoing to SDRT, particularly in sub-total resection. ConclusionIn our experience, a reduction of radiation dose schedule does not seem to jeopardize survival in methylated-MGMT patients independently by the extent of resection.A therapeutic approach to a standard reduction of RT dose for the methylated subset of patients may be feasible and could deserve prospective trials for validation.

Hyaluronate gel injection for rectum dose reduction in gynecologic high-dose-rate brachytherapy: initial Japanese experience.

Perirectal hyaluronate gel injection (HGI) appears to be a promising technique for healthy tissue dose sparing in pelvic radiotherapy. In this analysis, we report our initial experience of HGI in gynecologic brachytherapy, focusing on its safety and effectiveness for dose reduction to the rectum. Between July 2013 and May 2014, 36 patients received HGI for primary/salvage gynecologic brachytherapy. Dosimetric effect analysis was based on pre- and post-HGI computed tomography dataset registration with corresponding dose–volume histogram evaluation. The maximum dose to the most exposed 0.1 cm3 (D0.1cm3) and 2.0 cm3 (D2.0cm3) were used as index values for rectum and bladder dose evaluation. The dose indexes for target volume (TV) coverage were TV D90/V100. In all cases, HGI was well tolerated, with no acute or late adverse events documented at a median follow-up of 220 days (range, 18–1046 days). Rectum D2.0cm3 and D0.1cm3 were significantly decreased by HGI (P < 0.001 and P = 0.003, respectively), with no significant impact on dosimetric parameters of bladder and TV coverage. Factors correlating negatively with the dosimetric effect of HGI were an increasing number of interstitial catheters (P = 0.003) as well as Lcranial100% (P = 0.014) and Lcranial80% (P = 0.001) [i.e. the length from the anal verge to the most cranial point at which the 100% and 80% isodose lines, respectively, crossed the rectum]. The concept of HGI for gynecologic brachytherapy is plausible, and our initial experience indicates it to be an effective technique for rectal dose reduction in radiotherapy of intrapelvic tumours.

PO-0999 Functional Avoidance planning allows for lung dose reduction in radiotherapy of lung cancer

PO-0999 Functional Avoidance planning allows for lung dose reduction in radiotherapy of lung cancer

The rationale for HPV-related oropharyngeal cancer de-escalation treatment strategies.

The treatment paradigms for head and neck squamous cell cancer (HNSCC) are changing due to the emergence of human papillomavirus-associated tumors (HPV-related), possessing distinct molecular profiles and responses to therapy. Retrospective studies have suggested that HPV-related HNSCCs are more frequently cured than those caused by tobacco. Current clinical trials focus on the reduction of treatment-related toxicity and the development of HPV-targeted therapies. New treatment strategies include: 1) dose reduction of radiotherapy, 2) the use of cetuximab instead of cisplatin for chemo-radiation 3) less invasive surgical options, i.e. trans-oral robotic surgery and trans-oral laser microlaryngoscopy, and 4) more specific treatment attempts, including immunotherapeutic strategies, thanks to increasing comprehension of the molecular background of HPV-related HNSCC. Whereas recently published data shed light on immune mechanisms, other studies have focused on specific vaccination against HPV-related HNSCC. A crucial problem is patient selection to the chosen bias. Truly HPV-related cancers (p16-positive and HPV DNA-positive) with biomarkers for good response to therapy could be included in randomized trials aiming for less severe and better tailored therapy.

Feasibility of normal tissue dose reduction in radiotherapy using low strength magnetic field.

PurposeToxicity of mucosa is one of the major concerns of radiotherapy (RT), when a target tumor is located near a mucosal lined organ. Energy of photon RT is transferred primarily by secondary electrons. If these secondary electrons could be removed in an internal cavity of mucosal lined organ, the mucosa will be spared without compromising the target tumor dose. The purpose of this study was to present a RT dose reduction in near target inner-surface (NTIS) of internal cavity, using Lorentz force of magnetic field.Materials and MethodsTissue equivalent phantoms, composed with a cylinder shaped internal cavity, and adjacent a target tumor part, were developed. The phantoms were irradiated using 6 MV photon beam, with or without 0.3 T of perpendicular magnetic field. Two experimental models were developed: single beam model (SBM) to analyze central axis dose distributions and multiple beam model (MBM) to simulate a clinical case of prostate cancer with rectum. RT dose of NTIS of internal cavity and target tumor area (TTA) were measured.ResultsWith magnetic field applied, bending effect of dose distribution was visualized. The depth dose distribution of SBM showed 28.1% dose reduction of NTIS and little difference in dose of TTA with magnetic field. In MBM, cross-sectional dose of NTIS was reduced by 33.1% with magnetic field, while TTA dose were the same, irrespective of magnetic field.ConclusionRT dose of mucosal lined organ, located near treatment target, could be modulated by perpendicular magnetic field.

Systematic Review and Individual Patient Data Meta-Analysis Of Treatment-Related Risk Of Secondary Malignant Neoplasms After Hodgkin Lymphoma

IntroductionSecondary malignant neoplasms (SMN) are a major late effect of treatment for Hodgkin lymphoma (HL). Single trials have inadequate power to detect differences in SMN rates, while the many large-scale cohort-based studies of SMN after HL suffer from non-randomised, potentially biased comparisons of treatment strategies. The consequences of choice of first-line treatment for SMN risk remain unclear. We performed a Cochrane systematic review addressing this question based on our previous such review in 2000-2004. Material and methodsIndividual patient data (IPD) were collected from randomised controlled trials testing 5 currently relevant experimental strategies: avoidance of additional radiotherapy (RT) after chemotherapy (CT); reduction of RT field; reduction of RT dose; use of fewer CT cycles; intensification of CT regimen. All trials employed modern ABVD-like regimens and limited radiation fields, and recruited at least 50 patients per treatment group. Incidence of SMN, overall survival (OS) and progression-free survival (PFS) were analysed. Due to small numbers of events, SMN was analysed using Peto's method. Results and DiscussionData from 16 of the 21 eligible trials were obtained, including 9498 patients. These trials recruited between 1984 and 2007 and randomised between 100 and 1351 patients each. Standard chemotherapy was predominantly ABVD, followed by COPP/ABVD and MOPP/ABV. Most frequent intensified chemotherapies were escalated BEACOPP and Stanford V. For each study question, key information and resulting odds ratios are shown in the table. Avoidance of additional RT significantly reduced the SMN risk (Peto odds ratio 0.433, 95% confidence interval (0.28; 0.82), p=0.010). Intensified chemotherapy regimens were associated with a consistent slightly higher risk but the effect was not significant. Other study questions showed no marked effects on SMN risk. Regarding solid tumors, follow-up is still too short: an update after 5 to 10 years is necessary.Study questionNo. of trialsNo. of patients (total)Median follow-up (yr.)No. of SMNPeto odds ratio95% confidence intervalP-valueavoidance of RT (after CT)310117.8400.433(0.28; 0.82)0.010smaller RT field (after CT)4239710.81880.862(0.64; 1.16)0.32lower RT dose (after CT)329627.41101.032(0.71; 1.50)0.87fewer CT cycles324037.81011.096(0.74; 1.62)0.65intensified CT regimen729966.7911.37(0.89; 2.10)0.15 Disclosures:No relevant conflicts of interest to declare.

New treatment strategies for HPV-positive head and neck cancer

Epidemiological studies show an increasing incidence of human papilloma virus-associated oropharyngeal cancer. HPV-positive head and neck squamous cell carcinoma (HNSCC) is recognized as a special subgroup of HNSCC. Because HPV-positive patients are often younger and have an outstanding prognosis, long-term toxicities of therapy have become an important issue. Current clinical trials focus on a reduction of treatment-related toxicity and the development of HPV-specific therapies. New treatment strategies include a dose reduction of radiotherapy, the use of cetuximab instead of cisplatin for chemoradiation and transoral robotic surgery (TORS). Increasing comprehension of the molecular background of HPV-associated HNSCC has also lead to more specific treatment attempts including immunotherapeutic strategies. Whereas recently published data shed light on immune mechanisms resulting in a tolerogenic niche for HPV and HPV-associated HNSCC, other studies focus on specific vaccination of HPV-positive HNSCC. This study will summarize current therapy approaches and illustrate ongoing clinical trials in the field of HPV-positive HNSCC.

Radiation-induced hypopituitarism in children with acute lymphoblastic leukemia

Background:Acute Lymphoblastic Leukemia (ALL) is the most common malignancy among children for whom radiotherapy and chemotherapy are used for treatment. When hypothalamus-pituitary axis is exposed to radiotherapy, children's hormone level and quality of life are influenced. The aim of this study is to determine late effects of radiotherapy on hormonal level in these patients.Materials and Methods:In this study 27 children with ALL, who have been referred to Shahid Ramezanzadeh Radiation Oncology Center in Yazd-Iran and received 18-24 Gy whole brain radiation with Cobalt 60 or 9 MV linear accelerator, were assessed. These patient's basic weight, height and hormonal levels were measured before radiotherapy and also after different periods of time.Results:GHD (growth hormone deficiency) after clonidine stimulation test was observed in 44% (n=12) and that in 50% of them (n=6), less than 1 year, had been passed from their radiation therapy. None of these patients demonstrated hormone deficiency in other axes.Conclusions:This study showed that even application of a 18-24 Gy radiation dose might influence growth hormone levels; therefore, we recommend reduction of radiotherapy dose in such patients whenever possible.

Combination of bevacizumab and irradiation on uveal melanoma: an in vitro and in vivo preclinical study

Radiotherapy (RT) is the standard treatment for uveal melanoma. However it can cause damage to the retina and optic nerve. This study examined the in vitro and in vivo effects of the anti-VEGF monoclonal antibody bevacizumab associated with radiotherapy (RT) on tumor growth and tumor proliferation and vasculature on OCM-1 human uveal melanoma cell line. The anti-proliferative effects of bevacizumab, RT and their combination were tested both in vitro (OCM-1 cells co-cultured with HUVEC cells in Transwell plates) and in vivo (OCM-1 tumor xenografts in nude mice). In addition, treatment effects in vitro on VEGF secretion, as well as treatment effects in vivo on tumor proliferation (Ki67 labelling), tumor vasculature (VEGFR2 labelling) and VEGF tumoral concentration were analyzed. Bevacizumab given alone had a significant impact on tumor growth in vivo (and moderate effects in vitro). The bevacizumab-RT combination had additive effects in vitro (tumor cell proliferation) and in vivo (tumor growth), which translated into a significant decrease in Ki67 expression, VEGFR2 labelling and VEGF tumoral content. The bevacizumab-RT combination could be a promising clinical option to explore for the management of human uveal melanoma, since it may allow RT dose reduction without loss of antitumor efficacy.

Risk Stratification Treatment of Pediatric Rhabdomyosarcoma: South Egypt Cancer Institute Experience

Risk stratification allows tailoring of treatment protocol using, for selected patients, reduced total chemotherapy exposure, including decreases in alkylator therapy and avoidance of agents with recognized risk of late complications (anthracyclines), elimination of irradiation and reduction of radiotherapy dose. Patients and Methods: Twenty-nine newly diagnosed pediatric rhabdomyosarcoma patients attended the pediatric oncology department between January 2008 and May 2011. Patients were divided into 3 groups according to age, stage, group, pathology and site of the tumor. Treatment protocol tailored according to risk group. Results: Twenty-nine newly diagnosed pediatric rhabdomyosarcoma patients were evaluated. Seven patients had low risk, Intermediate risk included 12 patients, and 10 patients had high risk. After three years median follow up, event free survival was 51.7% for all patients however it was 86%, 67% and 10% for low, intermediate and high risk respectively (P = 0.0002). There was statistical difference for survival among different sites, histology, clinical group and stage as risk factors within each risk group, no statistically survival significance of any of these factors within the same risk group. Conclusion: Risk stratification is the best single predictor factor for pediatric rhabdomyosarcoma and allows tailoring of the treatment protocol. For selected patients, reductions in total chemotherapy exposure, elimination of irradiation in selected low risk patients and reduction of radiotherapy dose according to postoperative margin and nodal status is safe.