Photon-based Radiotherapy Research Articles

Intensity-modulated carbon-ion radiation therapy versus intensity-modulated photon-based radiation therapy in locally recurrent nasopharyngeal carcinoma: a dosimetric comparison.

PurposeTo identify the specific dose advantage of intensity-modulated carbon-ion radiation therapy (IMCT) over photon-based intensity-modulated radiation therapy (IMRT) in the treatment of locally recurrent nasopharyngeal carcinoma (NPC).Materials and methodsTen patients with locally recurrent NPC underwent IMCT and IMRT planning. Target definition followed the recommendations of the International Commission on Radiation Units and Measurements (ICRU) reports no. 50, 62 and 83. The real treatment plans which were delivered to patients were designed on the Siemens Syngo planning system while the control plans for dosimetric comparison were generated from the Varian Medical Systems. The optimization constraints of the two designs were basically the same. Target coverage was evaluated using the following parameters: Dmin, Dmax, D1, D2, D50, D95, D98 and D99. Target dose distribution and conformality were evaluated using the homogeneity index and conformity index. Normal tissue sparing of organs at risk (OARs) were evaluated using Dmean, D1 and Dmax. SPSS 22.0 software was used for data analysis.ResultsBoth IMCT and IMRT plans met clinical prescription dose requirements. Target coverage of D1, D2, D50, D95, D98, D99 were not significantly different between the two plans (P>0.05). The two plans showed satisfactory coverage of the target without significant difference. There was no significant difference in terms of the homogeneity and conformability between the two plans. Dosimetric parameters for the brain stem, spinal cord, parotid gland, optic chiasm, eyeball, lens, temporal lobe and inner ear were significantly reduced in the IMCT plan (P<0.05).ConclusionAs compared with photon-based IMRT, IMCT significantly reduces radiation dose to the OARs in the treatment of locally recurrent NPC while maintaining the dose coverage to the target volumes. Such a feature is particularly important for patients who experienced previous high-dose irradiation.

Normal tissue complication probability models in plan evaluation of children with brain tumors referred to proton therapy

Background: Children with brain tumors undergoing radiotherapy are at particular risk of radiation-induced morbidity and are therefore routinely considered for proton therapy (PT) to reduce the dose to healthy tissues. The aim of this study was to apply pediatric constraints and normal tissue complication probability (NTCP) models when evaluating the differences between PT and contemporary photon-based radiotherapy, volumetric modulated arc therapy (VMAT).Methods: Forty patients (aged 1–17 years) referred from Norwegian institutions to cranial PT abroad during 2014–2016 were selected for VMAT re-planning using the original CT sets and target volumes. The VMAT and delivered PT plans were compared by dose/volume metrics and NTCP models related to growth hormone deficiency, auditory toxicity, visual impairment, xerostomia, neurocognitive outcome and secondary brain and parotid gland cancers.Results: The supratentorial brain, temporal lobes, hippocampi, hypothalamus, pituitary glands, cochleas, salivary glands, optic nerves and chiasm received lower mean doses from PT. Reductions in population median NTCP were significant for auditory toxicity (VMAT: 3.8%; PT: 0.3%), neurocognitive outcome (VMAT: 3.0 IQ points decline at 5 years post RT; PT: 2.5 IQ points), xerostomia (VMAT: 2.0%; PT: 0.6%), excess absolute risk of secondary cancer of the brain (VMAT: 9.2%; PT: 6.7%) and salivary glands (VMAT: 2.8%; PT:0.5%). Across all patients, 23/38 PT plans had better or comparable estimated risks for all endpoints (within ±10% of the risk relative to VMAT), whereas for 1/38 patients all estimates were better or comparable with VMAT.Conclusions: PT reduced the volumes of normal tissues exposed to radiation, particularly low-to-intermediate dose levels, and this was reflected in lower NTCP. Of the included endpoints, substantial reductions in population medians were seen from the delivered PT plans for auditory complications, xerostomia, and risk of secondary cancers of the brain and salivary glands.

Particle therapy for prostate cancer: The past, present and future.

Although prostate cancer control using radiotherapy is dose‐dependent, dose–volume effects on late toxicities in organs at risk, such as the rectum and bladder, have been observed. Both protons and carbon ions offer advantageous physical properties for radiotherapy, and create favorable dose distributions using fewer portals compared with photon‐based radiotherapy. Thus, particle beam therapy using protons and carbon ions theoretically seems suitable for dose escalation and reduced risk of toxicity. However, it is difficult to evaluate the superiority of particle beam radiotherapy over photon beam radiotherapy for prostate cancer, as no clinical trials have directly compared the outcomes between the two types of therapy due to the limited number of facilities using particle beam therapy. The Japanese Society for Radiation Oncology organized a joint effort among research groups to establish standardized treatment policies and indications for particle beam therapy according to disease, and multicenter prospective studies have been planned for several common cancers. Clinical trials of proton beam therapy for intermediate‐risk prostate cancer and carbon‐ion therapy for high‐risk prostate cancer have already begun. As particle beam therapy for prostate cancer is covered by the Japanese national health insurance system as of April 2018, and the number of facilities practicing particle beam therapy has increased recently, the number of prostate cancer patients treated with particle beam therapy in Japan is expected to increase drastically. Here, we review the results from studies of particle beam therapy for prostate cancer and discuss future developments in this field.

Testosterone Levels and Sexual Quality of Life After Stereotactic Body Radiation Therapy for Prostate Cancer: A Multi-Institutional Analysis of Prospective Trials

The impact of higher scatter doses per fraction on testicular function and quality of life after prostate stereotactic body radiation therapy (SBRT) is poorly studied. Six hundred thirty-six patients treated with SBRT for low- to intermediate-risk prostate cancer from 2009 to 2014 were included. Changes in testosterone and in sexual and hormonal domain scores on the Expanded Prostate Cancer Index Composite-26 (EPIC) questionnaire over a 24-month period were evaluated via a 1-sided t test. EPIC score changes were evaluated in comparison with a distribution-based minimal clinically important difference threshold, wherein changes of greater than one half or greater than one third of the standard deviation in each domain were considered as medium-sized or small-sized effects, respectively. Median and mean percent changes in testosterone at the 3- to 6-month, 7- to 12-month, 13- to 18-month, and 19- to 24-month time periods were -13.41% and -4.49% (P = .02); -12.23% and -2.77% (P = .13); -11.20% and -0.29% (P = .47); -5.00% and + 1.20% (P = .65). When analyzed after dividing the cohort into 3 groups based on baseline testosterone values using tertiles, testosterone tended to increase in patients in the first group and decrease in patients in the third group. Overall, the decline in EPIC hormonal domain scores never exceeded the threshold for a small-sized effect, though the decline in EPIC sexual domain scores did pass this threshold at the 19- to 24-month time period (mean 10.90 point decline). This decline was not present when groups were examined individually. In this large cohort of prospectively followed patients, there was a transient decline in testosterone shortly after SBRT that normalized by 24 months posttreatment. There was no significant change in EPIC hormonal domain scores. A significant decline in EPIC sexual domain scores, consistent with a small-sized clinically detectable difference, manifested between 19 and 24 months of follow-up. These results are consistent with testosterone decline patterns and sexual function changes seen after other forms of photon-based radiation therapy.

The Promise of Proton Therapy for Central Nervous System Malignancies.

Radiation therapy plays a significant role in management of benign and malignant diseases of the central nervous system. Patients may be at risk of acute and late toxicity from radiation therapy due to dose deposition in critical normal structures. In contrast to conventional photon delivery techniques, proton therapy is characterized by Bragg peak dose deposition which results in decreased exit dose beyond the target and greater sparing of normal structure which may reduce the rate of late toxicities from treatment. Dosimetric studies have demonstrated reduced dose to normal structures using proton therapy as compared to photon therapy. In addition, clinical studies are being reported demonstrating safety, feasibility, and low rates of acute toxicity. Technical challenges in proton therapy remain, including full understanding of depth of proton penetration and the biological activity in the distal Bragg peak. In addition, longer clinical follow-up is required to demonstrate reduction in late toxicities as compared to conventional photon-based radiation techniques. In this review, we summarize the current clinical literature and areas of active investigation in proton therapy for adult central nervous system malignancies.

Protons versus Photons for Unresectable Hepatocellular Carcinoma: Liver Decompensation and Overall Survival

Ablative radiation therapy is increasingly being used for hepatocellular carcinoma (HCC) resulting in excellent local control rates; however, patients without evidence of disease progression often die from liver failure. The clinical benefit of proton- over photon-based radiation therapy is unclear. We therefore sought to compare clinical outcomes of proton versus photon ablative radiation therapy in patients with unresectable HCC. This is a single-institution retrospective study of patients treated during 2008 to 2017 with nonmetastatic, unresectable HCC not previously treated with liver-directed radiation therapy and who did not receive further liver-directed radiation therapy within 12months after completion of index treatment. The primary outcome, overall survival (OS), was assessed using Cox regression. Secondary endpoints included incidence of non-classic radiation-induced liver disease (defined as increase in baseline Child-Pugh score by ≥2 points at 3months posttreatment), assessed using logistic regression, and locoregional recurrence, assessed using Fine-Gray regression for competing risks. All outcomes were measured from radiation start date. The median follow-up was 14months. Of 133 patients with median age 68years and 75% male, 49 (37%) were treated with proton radiation therapy. Proton radiation therapy was associated with improved OS (adjusted hazard ratio, 0.47; P=.008; 95% confidence interval [CI], 0.27-0.82). The median OS for proton and photon patients was 31 and 14months, respectively, and the 24-month OS for proton and photon patients was 59.1% and 28.6%, respectively. Proton radiation therapy was also associated with a decreased risk of non-classic radiation-induced liver disease (odds ratio, 0.26; P=.03; 95% CI, 0.08-0.86). Development of nonclassic RILD at 3months was associated with worse OS (adjusted hazard ratio, 3.83; P<.001; 95% CI, 2.12-6.92). There was no difference in locoregional recurrence, including local failure, between protons and photons. Proton radiation therapy was associated with improved survival, which may be driven by decreased incidence of posttreatment liver decompensation. Our findings support prospective investigations comparing proton versus photon ablative radiation therapy for HCC.

Raman spectroscopy monitoring of MCF10A cells irradiated by protons at clinical doses

Purpose: Proton therapy has been recently proposed as a radiotherapy form for breast cancer treatment in view of its potentially decreased normal-tissue toxicity compared with conventional photon-based radiotherapy. However, the risks for the healthy tissue cannot be completely eliminated. In the present study, the suitability of Raman spectroscopy to monitor the radiosensitivity of normal cells exposed to clinical proton beam was investigated.Materials and methods: MCF10A normal human breast cells were irradiated at two different proton doses: 0.5 Gy and 4 Gy. They were fixed immediately after irradiation and measured by means of Raman spectroscopy technique. The obtained data were analyzed both by evaluating the intensity ratio of specific Raman spectral peaks and through Multivariate Distance Matrix Regression technique.Results: Certain Raman peaks associated with DNA showed a systematic suppression at both dose levels. In particular, the intensity of a Raman peak at 784 cm−1, related to a stretching mode inside the phosphate group of DNA, is very sensitive to the proton beam exposure, even at the lowest investigated dose. Therefore, it could be considered as a spectral marker of cytogenetic damage.Conclusions: The obtained results are encouraging for the future of Raman spectroscopy in radiobiology research, particularly for improving risk assessment in the field of proton radiotherapy. Specifically, these findings validate Raman spectroscopy to measure biological response in human breast cells exposed to standard proton therapy doses used in clinical setting.

Proton therapy for skull base tumors: A review of clinical outcomes for chordomas and chondrosarcomas.

Skull base chordomas and chondrosarcomas are rare tumors traditionally treated by surgical resection and adjuvant radiation therapy (RT). We will discuss data evaluating clinical outcomes of proton therapy in the treatment of skull base chordomas and chondrosarcomas. A literature review was performed using a MEDLINE search from January 1990 to January 2017. The published data suggest that the dose intensification allowed by proton therapy has resulted in good clinical outcomes and a tolerable toxicity profile. Proton therapy is a modern RT technique that has demonstrated improved preliminary clinical outcomes in the treatment of skull base chordomas and chondrosarcomas compared to conventional radiotherapy, and comparable to other advanced photon-based RT techniques.

Intensity modulated proton therapy (IMPT) – The future of IMRT for head and neck cancer

Radiation therapy plays an integral role in the management of head and neck cancers (HNCs). While most HNC patients have historically been treated with photon-based radiation techniques such as intensity modulated radiation therapy (IMRT), there is a growing awareness of the potential clinical benefits of proton therapy over IMRT in the definitive, postoperative and reirradiation settings given the unique physical properties of protons. Intensity modulated proton therapy (IMPT), also known as “pencil beam proton therapy,” is a sophisticated mode of proton therapy that is analogous to IMRT and an active area of investigation in cancer care. Multifield optimization IMPT allows for high quality plans that can target superficially located HNCs as well as large neck volumes while significantly reducing integral doses. Several dosimetric studies have demonstrated the superiority of IMPT over IMRT to improve dose sparing of nearby organs such as the larynx, salivary glands, and esophagus. Evidence of the clinical translation of these dosimetric advantages has been demonstrated with documented toxicity reductions (such as decreased feeding tube dependency) after IMPT for patients with HNCs. While there are relative challenges to IMPT planning that exist today such as particle range uncertainties and high sensitivity to anatomical changes, ongoing investigations in image-guidance techniques and robust optimization methods are promising. A systematic approach towards utilizing IMPT and additional prospective studies are necessary in order to more accurately estimate the clinical benefit of IMPT over IMRT and passive proton therapy on a case-by-case basis for patients with sub-site specific HNCs.

Radiotherapy Advances in Pediatric Neuro-Oncology.

Radiation therapy (RT) represents an integral component in the treatment of many pediatric brain tumors. Multiple advances have emerged within pediatric radiation oncology that aim to optimize the therapeutic ratio—improving disease control while limiting RT-related toxicity. These include innovations in treatment planning with magnetic resonance imaging (MRI) simulation, as well as increasingly sophisticated radiation delivery techniques. Advanced RT techniques, including photon-based RT such as intensity-modulated RT (IMRT) and volumetric-modulated arc therapy (VMAT), as well as particle beam therapy and stereotactic RT, have afforded an array of options to dramatically reduce radiation exposure of uninvolved normal tissues while treating target volumes. Along with advances in image guidance of radiation treatments, novel RT approaches are being implemented in ongoing and future prospective clinical trials. As the era of molecular risk stratification unfolds, personalization of radiation dose, target, and technique holds the promise to meaningfully improve outcomes for pediatric neuro-oncology patients.

I007] Treatment planning in proton therapy

Purpose To present the most important physics aspects of proton therapy (PT) treatment planning for scanning beams and compare them with photon-based radiotherapy. Methods The most important differences of protontherapy treatment planning with pencil beam scanning (PBS) with respect to what is considered now the norm in radiotherapy with photons (XRT) are the following: 1) The dosimetric inaccuracies in the map of proton stopping power (PSP) estimated via CT imaging are larger than similar error in estimating electron density for photons. This is the reason behind the development of more refined methods (e.g. dual energy CT or proton CT) and the current impossibility of MR-based protontherapy; 2) The pristine beam is in principle simpler to model than in photons, as no beam modifiers are used to shape the beam, with one significant exception: the preabsorber (aka “range shifter”); 3) Up until recently, dose calculation was performed with pencil beam-based algorithms. Now a transition is happening towards Monte Carlo-based algorithms, however for reasons that are different than in XRT; 4) In XRT geometrical uncertainties are handled during planning with ad hoc volume such as the planning target volume (PTV). In PT this approach is hardly satisfactory, albeit still common, and most advanced planning solutions are in fact based on PTV-less so called “robust optimization”, where the effect of range and setup uncertainties is essentially part of the cost function. This leaves open the issue of dose reporting, which is now approached in different ways at different PT centers; 5) PT treatment planning is performed assuming a constant 1.1 relative biological effectiveness (RBE) of protons with respect to XRT. This is an approximation, and the need of variable RBE in proton planning is one of the “hot topic” at the moment; 6) Adaptive therapy, and as a consequence adaptive treatment planning, is an area of development that has to be explored further. PT may be a field where the concept of “online adaptive” may have a clinical impact, but the times are still premature for a large scale implementation of these techniques.

A treatment planning comparison of contemporary photon-based radiation techniques for breast cancer.

Background and purposeAdjuvant radiation therapy (RT) of the whole breast (WB) is still the standard treatment for early breast cancer. A variety of radiation techniques is currently available according to different delivery strategies. This study aims to provide a comparison of six treatment planning strategies commonly adopted for breast-conserving adjuvant RT and to use the Pareto concept in an attempt to assess the degree of plan optimization.Materials and methodsTwo groups of six left- and five right-sided cases with different dose prescriptions were involved (22 patients in total). Field-in-Field (FiF), two and four Fields static-IMRT (sIMRT-2f and sIMRT-4f), Volumetric-Modulated-Arc-Therapy (VMAT), Helical Tomotherapy (HT) and Static-Angles Tomotherapy (TomoDirect™ – TD) were planned. Dose volume constraints were taken from the RTOG protocol 1005. Pareto fronts were built for a selected case to evaluate the reliability of the plan optimization process.ResultsThe best target dose coverage was observed for TD able to improve significantly (p < 0.01) the V95% in a range varying from 1.2% to 7.5% compared to other techniques. The V105% was significantly reduced up to 2% for HT (p < 0.05) although FiF and VMAT produced similar values. For the ipsilateral lung, V5Gy, V10Gy and Dmean were significantly lower than all other techniques (p < 0.02) for TD while the lowest value of V20Gy was observed for HT. The maximum dose to contralateral breast was significantly lowest for TD (p < 0.02) and for FiF (p < 0.05). Minor differences were observed for the heart in left-sided patients. Plans for all tested techniques were found to lie on their respective Pareto fronts.ConclusionsOverall, TD provided significantly better results in terms of target coverage and dose sparing of ipsilateral lung with respect to all other evaluated techniques. It also significantly minimized dose to contralateral breast together with FiF. Pareto front analysis confirmed the reliability of the optimization for a selected case.

Acoustic Analog Front End for Proton Range Detection in Hadron Therapy

Clinical ions beams for cancer treatment provide maximum energy deposition (Bragg peak (BP)) at the end of their range and practically no dose behind. This enables a more efficient therapeutic option comparing with classical photon-based radiotherapy where maximum energy is deposited at the body interface. Obviously, minimum-error BP detection is, thus, a key aspect of this treatment. This paper investigates a promising detection technique, based on the so-called ionoacoustic effect. The BP energy deposition causes a small (millikelvin) heating of the surrounding volume that in turn induces a pressure variation. This generates a sound signal that can be detected by an acoustic sensor placed at a certain distance from the BP point. Thus, the sound time-of-flight measure aims, with sound speed, to detect the BP position with very high accuracy (<1mm). This paper presents the results of a complete cross-domain model that starting from proton beam energy provides the induced pressure variation in water, emulates the propagation of sound waves in the medium, and finally, returns a voltage signal whose time evolution determines BP position with an average deviation from effective position of 1% accuracy.

(OA11) Timing of Radiotherapy for Pediatric Patients With Parameningeal Rhabdomyosarcoma With Intracranial Extension

This study was designed to assess clinical outcomes and patterns of failure, particularly as regards the timing of radiotherapy (RT), for pediatric patients with parameningeal rhabdomyosarcoma with intracranial extension (ICE-PM-RMS). Patients with ICE-PM-RMS have high rates of local and central nervous system (CNS) relapse, and historically have been treated with RT at week 0 of chemotherapy to improve disease-related outcomes. The recently-completed Children’s Oncology Group (COG) ARST0531 trial delayed RT for these patients to week 4, and the ongoing COG protocol ARST1431 is further deferring RT until week 13 of chemotherapy. With limited data available on the effect of such a delay in RT for ICE-PM-RMS patients, we sought to characterize our own experience treating ICE-PM-RMS, and determine the effect of RT timing on outcomes. Between 2006 and 2015, 15 consecutive patients with ICE-PM-RMS were treated at a single institution with RT as part of combined modality therapy using RT and chemotherapy. All patients had radiographic evidence of intracranial extension by MRI; patients with leptomeningeal disease (LMD) at diagnosis were excluded. RT was delivered using proton-beam therapy (11/15 patients, 73%) or photon-based RT (4/15 patients, 27%), to a median dose of 50.4Gy(RBE) to the primary tumor site. RT was initiated at or before week 4 of chemotherapy in 5 patients (33%), and after week 4 in 10 patients (67%). The primary reason for RT initiation after week 4 was referral delay. Five-year overall survival and progression-free survival for the entire cohort were 51.4% and 40.0%, respectively. Nine patients (60%) experienced disease recurrence, all of whom had a combination of LMD and/or in-field local relapse with intracranial component. No patient who initiated RT by week 4 experienced relapse (0/5 patients, 0%), whereas 9 patients who initiated RT after week 4 experienced failure (9/10 patients, 90%, Fisher’s exact test p=0.002). RT timing was a significant predictor of both progression-free survival (PFS, hazard ratio [HR] 7.79, 95% confidence interval [CI] 2.02 – 29.98, log-rank test p=0.003) and overall survival (HR 6.92, CI 1.49 – 32.08, p=0.01). Other disease and treatment characteristics such as tumor size, choice of chemotherapy regimen, and response to induction chemotherapy did not predict PFS. Early initiation of local therapy (by week 4) for ICE-PM-RMS patients appears to be critical for both disease control and survival. These data raise concerns regarding the current COG trial ARST1431, in which non-metastatic ICE-PM-RMS patients will be treated with RT at week 13 after chemotherapy initiation. Our findings suggest ICE-PM-RMS patients on this protocol may be at risk for poorer outcomes as a result of this change in RT timing compared with prior cooperative group studies.

Considerations when treating lung cancer with passive scatter or active scanning proton therapy.

Lung cancer, due to its poor clinical outcomes and significant toxicity associated with standard photon-based radiation, is a disease site that has the potential to greatly benefit from accurate treatment with proton radiation therapy. The potential of proton therapy is the ability to increase the radiation dose to the tumor while simultaneously decreasing the radiation dose to surrounding healthy tissues. For lung cancer treatment, this could mean significant sparing of the uninvolved healthy lung, which is difficult to achieve with external photon beam therapy, or decreasing the heart dose. In treating lung cancer with proton therapy, some additional considerations need to be made compared to treating patients with external photon beam radiation therapy. These include accounting for the finite range of protons in the patient, understanding temporal effects, potential dose discrepancies and choosing an appropriate treatment planning system for the task. One final consideration is differences between the different available proton therapy delivery systems-passive scattered proton therapy (PSPT) and active scanning proton therapy.

The evolution of practical radiobiological modelling.

A summary of the key aspects of radiobiological modelling is provided, based on the theoretical and practical concepts of the linear quadratic model, which gradually replaced other numerical approaches. The closely related biological effective dose concept is useful in many clinical applications. Biological effective dose formulations in conventional photon-based radiotherapy continue to be developed, and can be extended to the now increasingly used proton and ion-beam therapy, to very low or high dose ranges, the dose rate effect, hypoxia and repopulation. Such established and new research developments will be of interest to clinicians, physicists and biologists to better understand the processes underlying radiotherapy and assist their collaborative efforts to make radiotherapy safer and more effective.

Late Effects After Radiotherapy for Childhood Low-grade Glioma.

This single-institution report describes long-term disease control and late effects in pediatric patients with low-grade glioma (LGG) following radiotherapy (RT). Twenty-nine pediatric patients with LGG were treated with photon-based RT from 1970 to 2004 (mean age at time of RT, 9.8 y; range, 0.6 to 19 y). One patient underwent gross total resection, 25 underwent subtotal resection or biopsy, and 3 were treated based on radiographic characteristics alone. Three patients underwent chemotherapy before RT. The median RT dose was 54 Gy (range, 40 to 55 Gy). The median follow-up was 17.8 years (range, 1.6 to 36.8 y) for all patients and 19.9 years (range, 1.6 to 36.8 y) for all living patients. The 5-, 10-, and 20-year local control and progression-free survival rates were equivalent at 82%, 74%, and 63%, respectively. The 5-, 10-, and 20-year cause-specific survival and overall survival rates were equivalent at 89%, 85%, and 58%, respectively. On univariate analysis, age below 4 years during treatment was associated with significantly inferior local control (P=0.0067), cause-specific survival (P=0.0021), and overall survival (P=0.0021). Of the 23 survivors analyzed for late toxicity, 15 (65%) developed grade 3+ toxicity. The most common Common Terminology Criteria for Adverse Events grade 3 toxicity (30% of survivors) was serious cognitive disability. Four patients (14%) died secondary to treatment complications, all occurring over a decade after completing RT. Over half of children diagnosed with LGG survive >20 years after RT; this report reveals the chronicity of toxicity beyond the typically reported follow-up. Our findings inform the therapeutic ratio of RT in this disease and may help guide late-effect screening recommendations.

The relative biological effectiveness of proton and carbon ion beams in photon-sensitive and resistant nasopharyngeal cancer cells

Background: Approximately 10–15% of all nasopharyngeal carcinoma (NPC) cases will develop local recurrence (LR) after definitive radiation therapy. Clinical data has demonstrated a decreased treatment-related toxicities and a potential improved local control rate with carbon ion radiotherapy (CIRT) as compared to photon-based intensity-modulated radiotherapy (IMRT) for LR-NPC. However, the relative biological effectiveness (RBE) for NPC cells, especially the photon-radioresistant nasopharyngeal carcinoma (prNPC) cells within recurrent tumors, have not been determined. Methods: An established prNPC cell line (CNE-2R), which represents a cell model for extremely photon resistant NPC, and its parental cell line, CNE-2 were irradiated by photons or protons (energy, 74.55– 95.8 MeV; LET, ~3.125 keV/μm) with doses of 2, 4, 6, 8 and 10 Gy or by carbon ion pencil beam (energy, 148.3–180.3 MeV/u; LET, ~315.7 keV/μm) with physical doses of 2, 4, 6 and 8 Gy. Clonogenic survival was studied by analyzing the macrocolony formation and RBE values were at 10% (D 10 ) and 37% (D 37 ) survival. Results: For photon response, the α/β ratio for CNE-2 cells is higher compared to CNE-2R cells. The proton-treated cell survival curves demonstrated similar profiles to those of X-rays for CNE-2 and CNE-2R cell lines. The RBE of proton beam at 10% survival (D 10 ) was 0.95 for CNE-2 cells as compared with 0.98 for CNE-2R cells. The surviving fraction (SF) at 2 Gy, after exposure to photons, ~3.125 keV/μm protons and 315.7 keV/μm carbon ions, were 0.547, 0.566 and 0.166 for CNE-2 and 0.686, 0.750 and 0.310 for CNE-2R cells, respectively. The CNE-2R cells were less sensitive to carbon ions than CNE-2 cells. The RBE for carbon at 10% and 37% survival levels were 2.46 and 2.90 for CNE-2 cells compared with 1.95 and 2.53 for CNE-2R cells, respectively. Therefore, the RBEs in the photon-resistant CNE-2R cells were relatively lower than those in photon-sensitive CNE-2 cells following X-ray or carbon ion irradiation at 315.7 keV/μm. Conclusions: Compared with photons and protons, carbon ion shows better cell inactivation capability in both CNE-2 cells and photon resistant CNE-2R cells. The RBE values of NPC cells can help in making strategic decisions on the design of clinical trials using carbon ion therapy.

Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy

Background and purposeCirculating lymphocytes are exquisitely sensitive to radiation exposure, even to low scattered doses which can vary drastically between radiation modalities. We compared the relative risk of radiation-induced lymphopenia between intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT) in esophageal cancer (EC) patients undergoing neoadjuvant chemoradiation therapy (nCRT). Material and methodsEC patients treated with IMRT and PBT were propensity matched based on key clinical variables. Treatment-associated lymphopenia was graded using CTCAE v.4.0. Using matched cohorts, univariate and multivariable multiple logistic regression was used to identify factors associated with increased risk of grade 4 lymphopenia as well as characterize their relative contributions. ResultsAmong the 480 patients treated with nCRT, 136 IMRT patients were propensity score matched with 136 PBT patients. In the matched groups, a greater proportion of the IMRT patients (55/136, 40.4%) developed grade 4 lymphopenia during nCRT compared with the PBT patients (24/136, 17.6%, P < 0.0001). On multivariable analysis, PBT was significantly associated with a reduction in grade 4 lymphopenia risk (odds ratio, 0.29; 95% confidence interval, 0.16–0.52; P < 0.0001). ConclusionPBT is associated with significant risk reduction in grade 4 lymphopenia during nCRT in esophageal cancer.

Quality of Life and Patient-Reported Outcomes Following Proton Radiation Therapy: A Systematic Review.

As costs of cancer care rise, the importance of documenting value in oncology increases. Proton beam radiotherapy (PBT) has the potential to reduce toxicities in cancer patients, but is relatively expensive and unproven. Evaluating quality of life (QOL) and patient-reported outcomes (PROs) is essential to establishing PBT's "value" in oncologic therapy. The goal of this systematic review was to assess QOL and PROs in patients treated with PBT. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic searches were conducted. The PubMed search engine was the primary data source, along with publications found from references of selected articles, and articles known to the authors published through 2017. Seventeen original investigations were found to have sufficient focus and relevance to be incorporated into the systematic review. Studies of skull base (n = 1), brain (n = 1), head/neck (n = 1), lung (n = 1), breast (n = 2), prostate (n = 8), and pediatric (n = 3) malignancies treated with PBT that met eligibility criteria were included. QOL did not deteriorate during PBT for skull base and after PBT for brain tumors, respectively. PROs were higher for PBT than photon-based radiotherapy for both head/neck and lung cancer. Patient-reported breast cosmesis was appropriate after PBT and comparable to photon modalities. PBT in various settings of prostate cancer displayed an expected post-therapy decline; one study showed improved PROs (rectal urgency, bowel frequency) for PBT, and two others showed PROs/QOL comparable with other modalities. Pediatric studies demonstrated improvements in QOL during therapy, with additional increases thereafter. Based on limited data, PBT provides favorable QOL/PRO profiles for select brain, head/neck, lung, and pediatric cancers; measures for prostate and breast cancers were more modest. These results have implications for cost-effective cancer care and prudently designed QOL evaluation in ongoing trials, which are discussed. Future data could substantially change the conclusions of this review.