April 2020 : what did we learn ?

Last month, the impact of Covid-19 on cancer treatment has been discussed in many articles. Several more studies have also been published showing the benefits of Proton Therapy for Pediatric Ewing Sarcoma, Head & Neck, Oropharyngeal, Breast, Lung, Esophageal, and Prostate cancers, and for re-irradiation.

Read our selection.

COVID-19 : global consequences for oncology

This pandemic will undoubtedly change the way we work. But the oncology community is relentlessly devoted to the patients, and we will certainly weather this unprecedented storm !


Editorial| Volume 21, ISSUE 4, P467, April 01, 2020

COVID-19: global consequences for oncology
The Lancet Oncology



Challenges posed by COVID-19 to children with cancer

⚠️ Let’s get ready !
Let’s work all together and let’s optimize all our resources to make sure our young patients receive the right treatment at the right time !
👉 “The coming months will pose many further challenges, which might include accessibility to scarce resources, effects on drug manufacture and supply, and the effect on care of children with cancer from low-income and middle-income countries. Continued collaboration among the international pediatric oncology community is required to get through such uncertain times.”

Rishi S Kotecha
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30205-9/fulltext



Treating childhood cancer : a necessity not a choice

“Inadequate access to care, late diagnosis, financial toxicity, and poor-quality care are ubiquitous barriers for children with cancer worldwide and have a crucial impact on survival outcomes. Owing to population growth and inequitable access to cancer care, 80% of the global cancer burden–in terms of both incidence and mortality is estimated to fall on children in low-income and middle-income countries (LMICs)—a humanitarian situation that demands immediate attention.”

Allison Landman
David Collingridge
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30145-5/fulltext



Pediatric Ewing Sarcoma : Depending on the chest wall subregion, proton treatment has the potential to minimize pulmonary, cardiac, renal, and hepatic toxicity, as well as second malignancies.

👉 Target conformity and homogeneity indices are generally better for the IMPT plans with beam aperture.
👉 Doses to the lung, heart, and liver for all patients are substantially lower with the 3DPT and IMPT plans than those of IMRT plans.
👉 In the IMPT plans with large spot without beam aperture, some OAR doses are higher than those of 3DCPT plans. The integral dose of each photon IMRT plan ranged from 2 to 4.3 times of proton plans.
👉 Compared to IMRT, proton therapy delivers significant lower dose to almost all OARs and much lower healthy tissue integral dose. Compared to 3DCPT, IMPT with small beam spot size or using beam aperture has better dose conformity to the target.
👉 Treatment plan using the smaller beam spot with beam apertures provided the best combination of target coverage and OAR sparing.

Impact of different treatment techniques for pediatric Ewing sarcoma of the chest wall: IMRT, 3DCPT, and IMPT with/without beam aperture
Zhong Su et al.
https://aapm.onlinelibrary.wiley.com/doi/full/10.1002/acm2.12870#.XpmY6trKGJk.linkedin


For patients with HPV-positive oropharyngeal cancer, the predicted risk of secondary malignant neoplasms (SMN) is significantly reduced statistically for treatment with Intensity Modulated Proton Therapy (IMPT) compared with Intensity Modulated photon Radiation Therapy (IMRT).

👉 Although both modalities afforded good target coverage, IMPT plans were able to achieve improved healthy-tissue sparing : significant reductions in mean mandible, contralateral parotid, lung and skin organ equivalent doses with IMPT compared with IMRT plans (P < .001).
👉 This reduction in integral dose led to a predicted decrease of 436 additional cases of SMNs for every 10 000 patients/y (or 4 per 100 patients/y) for treatment with protons instead of photons

Predicted Secondary Malignancies following Proton versus Photon Radiation for Oropharyngeal Cancers – Jain et al
https://www.theijpt.org/doi/pdf/10.14338/IJPT-19-00076.1


Oropharyngeal cancer : proton therapy improves Patient-reported outcomes

👉 Intensity Modulated Proton Therapy is associated with improved Patient-reported outcomes, reduced percutaneous endoscopic gastrostomy -tube placement, hospitalization, and narcotic requirements.
👉 Mucositis, dysphagia, and pain were decreased with IMPT.
👉 Benefits were predominantly seen in patients treated definitively or with chemoradiotherapy.

Comparative analysis of acute toxicities and patient reported outcomes between intensity-modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) for the treatment of oropharyngeal cancer
Manzar et al.
https://www.sciencedirect.com/science/article/pii/S0167814020301195


Particle therapies, such as proton therapy or carbon ion therapy, proposed to reduce the burden of xerostomia in patients following chemoradiotherapy for HNSCC

👉 Particle therapies are especially able to reduce moderate to low dose exposure to the oral cavity (minor salivary glands), submandibular glands, and parotid glands with similar target coverage based on the physical properties of the Bragg peak energy deposition of these approaches.

Sticky stuff: xerostomia in patients undergoing head and neck radiotherapy-prevalence, prevention, and palliative care.
Snider JW 3rd, Paine CC 2nd Annals of Palliative Medicine, 25 Mar 2020 10.21037/apm.2020.02.36



Be aware of Radiation-Induced Cardiotoxicity (RIC), and support advanced delivery techniques

👉 Breast cancer
Based on available data, a clear relationship exists between whole-heart dose and risk of cardiac events following Radiotherapy for breast cancer with a significant increase in risk for left-sided breast cancer patients (…) Patients, with a particular focus on those with left-sided disease, should be evaluated for cardiac-sparing techniques, including but not limited to deep-inspiration breath hold (DIBH), gating, prone positioning, and/or proton therapy, to achieve the lowest dose possible.
👉 Thoracic Malignancies (Lung and Esophageal cancers)
Because of the anatomic proximity of these cancers to the heart, however, radiomodulatory techniques such as DIBH or gating may not be as helpful in reducing heart dose; thus, other techniques, such as proton therapy, may be needed.

Nichols et al.
Cardiotoxicity and Radiation Therapy: A Review of Clinical Impact in Breast and Thoracic Malignancies
https://appliedradiationoncology.com/articles/cardiotoxicity-and-radiation-therapy-a-review-of-clinical-impact-in-breast-and-thoracic-malignancies


For locally advanced esophageal cancer, ProtonTherapy (PBT) reduced the risk and severity of Adverse Eventss compared with IMRT while maintaining similar progression-free survival (PFS)

👉 The posterior mean total toxicity burden (TTB) was 2.3 times higher for IMRT (39.9; 95% highest posterior density interval, 26.2-54.9) than (PBT) (17.4; 10.5-25.0).
👉 The mean postoperative complications (POCs) score was 7.6 times higher for IMRT (19.1; 7.3-32.3) versus PBT (2.5; 0.3-5.2).
👉 The posterior probability that mean TTB was lower for PBT compared with IMRT was 0.9989, which exceeded the trial’s stopping boundary of 0.9942 at the 67% interim analysis.
👉 The 3-year PFS rate (50.8% v 51.2%) and 3-year overall survival rates (44.5% v 44.5%) were similar.

Randomized Phase IIB Trial of Proton Beam Therapy Versus Intensity-Modulated Radiation Therapy for Locally Advanced Esophageal Cancer
Lin SH, et al. J Clin Oncol. 2020;doi:10.1200/JCO.19.02503.



Re-irradiation with proton therapy is a safe and effective treatment in patients with recurrent glioblastoma

Proton therapy does not negatively effect on health-related quality of life (HRQOL), but rather it seems to preserve HRQOL until the time of disease progression :
👉 The treatment was associated with improvement or stability in most of the preselected HRQOL domains.
👉 Global health improved over time with a maximum difference of six points between baseline and 3-months follow-up.
👉 Social functioning and motor dysfunction improved over time with a maximum difference of eight and two points, respectively.
👉 Non-significant decrease in cognitive and emotional functioning.
👉 Fatigue remained stable during the analysis such as the other preselected domains.

Proton therapy re-irradiation preserves health-related quality of life in large recurrent glioblastoma
Scartoni et al.
https://link.springer.com/article/10.1007/s00432-020-03187-w



The high conformality and lack of exit dose with proton therapy offer significant advantages for reirradiation

👉 By decreasing dose to adjacent normal tissues, proton therapy can more safely deliver definitive instead of palliative doses of reirradiation, more safely dose escalate reirradiation treatment, and more safely allow for concurrent systemic therapy in the reirradiation setting.

Proton Reirradiation: Expert Recommendations for Reducing Toxicities and Offering New Chances of Cure in Patients With Challenging Recurrence Malignancies
Simone et al.


Rectal Hydrogel Spacer Improves Late Gastrointestinal Toxicity

👉 compared with rectal balloon immobilization, treatment with the hydrogel spacer significantly reduced the risk of clinically relevant (grade 2+), late rectal bleeding and was associated with a significantly lower decrease in patient-reported bowel quality of life
👉 “the rectal-sparing benefit of the hydrogel spacer, particularly for reducing late rectal bleeding, was even greater than expected. These findings can hold interest for urologists who counsel patients about their treatment options for localized prostate cancer,” added Dr. Ellis, professor and vice-chair of urology, University of Washington, Seattle.

Dinh TT et al.
Rectal Hydrogel Spacer Improves Late Gastrointestinal Toxicity Compared to Rectal Balloon Immobilization After Proton Beam Radiation Therapy for Localized Prostate Cancer: A Retrospective Observational Study.
https://www.ncbi.nlm.nih.gov/pubmed/32035187


Prostate cancer : Hydrogel spacer reduce the rectal dose

👉 Significant rectal dose reduction (P < 0.001) between the treatment plans on pre- and post-CT images were achieved for all modalities for D50%, D20% and D2%.
👉 In particular, the dose reduction of high-dose (D2%) ranges were : −40.61 ± 11.19 for proton therapy −32.44 ± 5.51 for CK −25.90 ± 9.89 for HT −13.63 ± 8.27 for VMAT −8.06 ± 4.19% for 3DCRT
👉 The results of this study demonstrated that all external radiotherapy modalities with hydrogel spacer could reduce the rectal dose.”

Comparison of rectal dose reduction by a hydrogel spacer among 3D conformal radiotherapy (3DCRT), volumetric-modulated arc therapy (VMAT), helical tomotherapy (HT), CyberKnife (CK) and proton therapy – Saito et al.
Journal of Radiation Research, rraa013, https://lnkd.in/dU9-Zcw

Figure : Typical dose distribution of SO(−) and SO(+) and the results of five modalities: (a) 3DCRT, (b) VMAT, (c) HT, (d) CK and (e) proton. The contour of the orange color illustrates the rectum.

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Takeaway from BJR Proton Therapy special feature

Targeting cancer stem cells: protons versus photons – Dini et al.

👉 preclinical data suggest that protons and photons differ in their biological effects on cancer stem cells, with protons offering potential advantages, although the heterogeneity of cancer stem cells and the different proton irradiation modalities make the comparison of the results not so easy. 

Is there a role for arcing techniques in proton therapy ? – Carabe-Fernandez et al.

👉 although Proton Arc Therapy (PAT) may not produce better physical dose distributions than intensity modulated proton therapy, the radiobiological considerations associated with particular PAT techniques could offer the possibility of an increased therapeutic index.

Proton minibeams—a springboard for physics, biology and clinical creativity – Avraham Dilmanian et al.

👉 Proton minibeam therapy (PMBT) is a form of spatially fractionated radiotherapy wherein broad beam radiation is replaced with segmented minibeams—either parallel, planar minibeam arrays generated by a multislit collimator or scanned pencil beams that converge laterally at depth to create a uniform dose layer at the tumor. By doing so, the spatial pattern of entrance dose is considerably modified while still maintaining tumor dose and efficacy. Recent studies using computational modeling, phantom experiments, in vitro and in vivo preclinical models, and early clinical feasibility assessments suggest that unique physical and biological attributes of PMBT can be exploited for future clinical benefit

FLASH and minibeams in radiation therapy: the effect of microstructures on time and space and their potential application to protontherapy – Mazal et al.

👉 the combination of FLASH and minibeams using proton beams, in spite of their complexity, may help to optimize the benefits of several or all the reviewed aspects, through the following concepts:
(1)  the intrinsic advantages of protons to reduce the integral mid and low doses, will be volumetrically combined in synergy with the FLASH and minibeam effects as a whole;
(2)  to reduce mid and high equivalent doses in critical organs around the tumour volume using the FLASH effect with high dose rates achievable with proton beams, both with passive or pencil beam approaches;
(3) to reduce healthy tissue complications by the minibeams space modulation in every beam path, where protons can be focalized with a steep penumbra and hence a high peak to valley ratio;
(4) to deliver an homogeneous dose to the target at any depth using the multiple scattering of proton minibeams in depth, and/or with multiple fields, or even setting a controlled inhomogeneous “vertex” doses escalation approach, optimizing intensity modulated proton therapy with robust solutions;
(5) to modify present approaches of immunological responses by the combination of concentration of lattice doses in very short time with a slight increase in LET, and the microstructure in time and space of both effects and
(6) to deliver single or hypofractionated treatments in very short time per fraction, facilitating the treatment of moving organs, specially when using pencil beam approaches and the associated risk of interplay effects, as well as the optimal use of minibeams with minimal risk of movement during the fraction.
Proton beams have in consequence one of the highest potentials to optimize the use of FLASH and Minibeams effects in radiation therapy, individually or in a synergistic combination.

Re-irradiation with protons or heavy ions with focus on head and neck, skull base and brain malignancies – Seidensaal et al.

👉 Re-irradiation can offer a potentially curative solution in case of progression after initial therapy; however, a second course of radiotherapy can be associated with an increased risk of severe side-effects. Particle therapy with protons and especially carbon ions spares surrounding tissue better than most photon techniques, thus it is of high potential for re-irradiation. Irradiation of tumors of the brain, head and neck and skull base involves several delicate risk organs, e.g. optic system, brainstem, salivary gland or swallowing muscles. Adequate local control rates with tolerable side-effects have been described for several tumors of these locations as meningioma, adenoid cystic carcinoma, chordoma or chondrosarcoma and head and neck tumors.

Reduced radiation-induced toxicity by using proton therapy for the treatment of oropharyngeal cancer – Meijer et al.

👉 proton therapy results in lower dose levels in multiple organs at risk, which translates into reduced acute toxicity (i.e. up to 3 months after radiotherapy), while preserving tumour control. Next to reducing mucositis, tube feeding, xerostomia and distortion of the sense of taste, protons can improve general well-being by decreasing fatigue and nausea. Proton therapy results in decreased rates of tube feeding dependency and severe weight loss up to 1 year after radiotherapy, and may decrease the risk of radionecrosis of the mandible.

Photons or protons for reirradiation in (non-)small cell lung cancer: Results of the multicentric ROCOCO in silico study – Troost et al.

👉 IMPT was able to statistically significantly decrease the radiation doses to the OARs. IMPT was superior in achieving the highest tumour dose while also decreasing the dose to the organs at risk.

Paediatric proton therapy – Thomas et al.

👉 Along with high cure rates, the rate of (late) toxicities is reduced using this radiotherapy modality


Articles cited above and many more are available in Proton therapy special feature, The British Journal of Radiology 2020 93:1107 

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Proton therapy: the current status of the clinical evidences – by Dongryul Oh

Precision and Future Medicine 2019

Proton Therapy Clinical Evidences – Dongryul Oh

The dosimetric advantages of proton therapy—compared with photon therapy—have been clearly defined in many comparison studies involving various tumor sites. There are now accumulating clinical data demonstrating that this dosimetric advantage can lead to better outcomes such as reduced RT toxicity and improved treatment outcomes. 

Pediatric Tumors

RT has an important role in treating pediatric tumors including central nervous system (CNS) tumors, extra-cranial sarcomas, neuroblastoma, and hematopoietic tumors. Long-term toxicities, including secondary malignancies, neurocognitive dysfunctions, growth and musculoskeletal problems, and cardiac problems, are major concerns in pediatric patients who undergo RT. There have been many efforts to reduce the RT dose and volume to avoid these RT-related toxicities.

Proton therapy is one of the best options to reduce unnecessary irradiation dose and volume in pediatric patients.

More than 30 pediatric tumor types were treated, mainly with curative intent: 48% were CNS, 25% extra-cranial sarcomas, 7% neuroblastoma, and 5% hematopoietic tumors

Head and Neck Tumors

Retrospective data have demonstrated better local control (LC) and overall survival (OS) with proton therapy than with photon therapy including IMRT and stereotactic body radiation therapy (SBRT).

Proton therapy has also demonstrated better survival rates in nasal cavity and paranasal sinus tumors.

In oropharyngeal cancers, proton therapy can reduce toxicity to normal tissues.

Proton therapy can also reduce toxicities in unilateral irradiation, such as in cases involving major salivary gland tumor and oral cavity cancers, because the exit dose of the proton beam is essentially negligible

CNS tumors

Cognitive impairment has been one of major concerns following RT for CNS tumors. Proton therapy has a potential benefit to reduce the irradiated dose to normal brain tissue to prevent cognitive dysfunction. In addition, a dose escalation could be possible in radioresistant brain tumors such as high-grade gliomas.

Gastrointestinal tumors

Proton therapy can spare the surrounding normal tissues when it is used to treat gastrointestinal tumors. In the management of hepatocellular carcinoma (HCC), it is very important to spare liver function. Because the liver is an organ with parallel functional subunit in the model of radiation response of normal tissues, liver toxicity is more sensitive to irradiated volume. Proton therapy has a major advantage in reducing the irradiated volume of remnant liver when irradiating the tumor. In many retrospective trials, proton therapy resulted in favorable outcomes.

Re-irradiation

Proton therapy has the advantage of irradiating the target while reducing the dose to the surrounding normal tissues; thus, it has a potential benefit in re-irradiation. Many retrospective studies investigating re-irradiation in various tumor sites have been reported.

Non-Small Cell Lung Cancer

Low-dose shower is a major risk for radiation pneumonitis (RP) when treating non-small cell lung cancer (NSCLC) with photon therapy. If the lateral beam placement is avoided to reduce the lung dose, the irradiated dose to heart is consequently increased and results in increased cardiac death in long-term follow-up. In many dosimetric studies, proton therapy demonstrated advantages in lung and heart dose compared with photon therapy. Several clinical studies have reported treatment outcomes and toxicities of proton therapy in early-stage disease, locally advanced disease, re-irradiation, and in postoperative settings 

Indications for Proton Therapy

American Society for Radiation Oncology (ASTRO)  has updated the recommendations for insurance coverage. The ASTRO recommendation is based on four selection criteria:

  1. a decrease in dose inhomogeneity in a large treatment volume is required to avoid an excessive dose “hotspot” within the treated volume to lessen the risk for excessive early or late normal tissue toxicity;
  2. the target volume is in close proximity to ≥1 critical structure(s), and a steep dose gradient outside the target must be achieved to avoid exceeding the tolerance dose to the critical structure(s);
  3. a photon-based technique would increase the probability of clinically meaningful normal tissue toxicity by exceeding an integral dose-based metric associated with toxicity;
  4. and, finally, the same or an immediately adjacent area has been previously irradiated, and the dose distribution in the patient must be carefully modelled to avoid exceeding the cumulative tolerance dose to nearby normal tissues.

Based on the above medical necessity requirements and published clinical data, group 1, which is recommended coverage is listed as follows:

  • ocular tumors, including intraocular melanomas;
  • skull base tumors, primary or metastatic tumors of the spine, where spinal cord tolerance may be exceeded with conventional treatment or where the spinal cord has previously been irradiated;
  • hepatocellular cancer;
  • pediatric tumors;
  • patients with genetic syndromes making total volume of radiation minimization crucial;
  • malignant and benign primary CNS tumors;
  • advanced and/or unresectable H&N cancers;
  • the paranasal sinuses and other accessory sinuses cancers;
  • non-metastatic retroperitoneal sarcomas;
  • and cases requiring re-irradiation.

Read the full study on Precision and Future Medicine 2019

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Proton therapy has the potential to reduce cardiac toxicities compared to photon therapy

Photon vs proton therapy for reduction of cardiac toxicities in locally advanced lung cancer

S. Teoh,F. Fiorini,B. George,K.A. Vallis,F. Van den Heuvel https://www.sciencedirect.com/science/article/pii/S0167814019323515

Proton therapy has the potential to reduce cardiac toxicities compared to photon therapy. This analysis suggests that patients with tumour extension to and below T7 vertebrae would benefit most from proton therapy over photon therapy. The absolute benefit is higher in patients with underlying cardiac disease.

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Proton therapy for cancer lowers risk of side effects

by Julia Evangelou Strait, Washington University School of Medicine

Proton therapy results in fewer side effects than traditional X-ray radiation therapy for many cancer patients, according to a new study led by Washington University School of Medicine in St. Louis and the Perelman School of Medicine at University of Pennsylvania. Even with reduced side effects, proton therapy resulted in cure rates similar to those of X-ray radiation therapy.

Proton therapy for cancer lowers risk of side effects
A new study led by Brian Baumann, M.D., of Washington University School of Medicine in St. Louis, found that proton therapy (bottom) is associated with fewer severe side effects than conventional X-ray radiation therapy (top) for many cancer patients. Credit: Brian Baumann/Mike Worful

The study is the first major side-by-side comparison of side effects related to proton therapy and X-ray radiation therapy. It included almost 1,500 patients receiving combined chemotherapy and radiation therapy for lung, brain, head and neck, gastrointestinal and gynecologic cancers that had not yet spread to other parts of the body. Such patients receive both radiation and chemotherapy, a treatment regimen that often cures nonmetastatic cancer. But it also causes severe side effects—such as difficulty swallowing, nausea and diarrhea—that reduce quality of life and can, in some cases, require hospitalization.

After controlling for differences between the groups, such as age and additional medical problems, the researchers found that patients receiving proton therapy experienced a two-thirds reduction in the relative risk of severe side effects within 90 days of treatment, compared with patients receiving X-ray radiation therapy. Forty-five of 391 patients receiving proton therapy experienced a severe side effect in the 90-day time frame (11.5 percent). In the X-ray radiation therapy group, 301 of 1,092 patients experienced a severe side effect in the same period (27.6 percent). Patient data on side effects were gathered as the trial was ongoing, rather than after the fact.

“Proton therapy was associated with a substantial reduction in the rates of severe acute side effects—those that cause unplanned hospitalizations or trips to the emergency room—compared with conventional photon, or X-ray, radiation for patients treated with concurrent radiation and chemotherapy,” said Baumann, an assistant professor of radiation oncology at Washington University and an adjunct assistant professor of radiation oncology at Penn. “The opportunity to reduce the risk of severe side effects for patients and thereby improve their quality of life is very exciting to me. While there have been other studies suggesting that proton therapy may have fewer side effects, we were somewhat surprised by the large magnitude of the benefit.”

The researchers focused their study on what are called grade 3 adverse events, which are severe enough to require hospitalization. These can include pain, difficulty swallowing that might result in weight loss, difficulty breathing, and nausea and diarrhea severe enough to cause dehydration.

The researchers also found no differences between the two groups in survival, suggesting that proton therapy was just as effective in treating the cancer even as it caused fewer side effects. Overall survival at one year for the proton therapy group was 83 percent of patients versus 81 percent for the X-ray radiation therapy group. This difference was not statistically significant.

This study is the first large review of data across several cancer types to show a reduced side-effect profile for proton therapy compared with X-ray radiation therapy for patients receiving combined chemotherapy and radiation. Both types of radiation therapy are approved by the Food and Drug Administration for cancer treatment. Protons are relatively heavy, positively charged particles that hit their target and stop. X-ray beams consist of photons, which are much smaller particles that have almost no mass, allowing them to travel all the way through the body, passing through healthy tissue on the way out.

https://medicalxpress.com/news/2019-05-proton-therapy-cancer-lowers-side.html

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Treatment of inoperable NSCLC with IMPT and concurrent chemotherapy achieves excellent disease control with tolerable toxicity.

Clinical outcomes after intensity-modulated proton therapy with concurrent chemotherapy for inoperable non-small cell lung cancer

Adnan Elhammali, Pierre Blanchard, Alison Yoder, Zhongxing Liao, Xiadong Zhang, X. Ronald Zhu, Pamela K. Allen, Melenda Jeter, James Welsh, Quynh-Nhu Nguyen

Highlights

Intensity modulated proton therapy is a highly conformal treatment option.•

Treatment of inoperable NSCLC with IMPT offers excellent disease local control.•

Treatment was well tolerated with no grade 4 or 5 toxicity.

Abstract

Background & purpose

We report disease control, survival, and toxicity in patients with advanced inoperable non-small cell lung cancer (NSCLC) receiving concurrent chemotherapy and intensity-modulated proton therapy (IMPT) at a single institution.

Material and methods

All patients were treated with IMPT with concurrent chemotherapy. Endpoints assessed were local, regional, and distant control, disease-free survival (DFS), and overall survival (OS).

Results

Fifty-one patients were enrolled with a median follow-up time of 23.0 months; 39 (76%) were treated with a simultaneous integrated boost to the gross tumor volume (GTV). The median GTV dose was 67.3 CGE and the median CTV dose was 60.0 CGE. Median OS and DFS times were 33.9 months and 12.6 months. The 3-year local control rate was 78.3%. Treatment was well tolerated, with a grade 3 toxicity rate of 18% (9 events: 4 esophagitis, 3 dermatitis, 1 esophageal stricture, and 1 fatigue) and no grade 4 or 5 toxicity. The most common grade 2 toxic effects were esophagitis (22 [43%]), dermatitis (16 [31%]), pain (15 [29%]), and fatigue (14 [27%]).

Conclusions

Treatment of inoperable NSCLC with IMPT and concurrent chemotherapy achieves excellent disease control with tolerable toxicity.

https://www.sciencedirect.com/science/article/pii/S0167814019301513

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A Novel Prospective Study Assessing the Combination of Photodynamic Therapy and Proton Radiation Therapy: Safety and Outcomes When Treating Malignant Pleural Mesothelioma

“The combination of priming the immune system with intraoperative photodynamic therapy and then delivering proton therapy may have worked synergistically to stimulate the patient’s immune system to better fight the cancer,” Simone said. “More research on a cellular level is needed.”

Proton therapy is a unique type of radiation therapy that can more precisely target tumors while better protecting nearby normal tissue from the harmful radiation effects.

Normal tissues beyond and before the tumor cells are better spared, leaving far fewer side effects for patients, which is especially important with lung-sparing pleurectomy and decortication surgery. 

With a diffuse tumor such as pleural mesothelioma covering a large surface, Simone believes proton therapy is considerably more beneficial than traditional photon therapy, including the intensity-modulated radiation therapy that is often used. 

“Given the ability of proton therapy to better protect normal tissues, no patient in the entire cohort experienced any notable acute or late toxicities,” he said. “It seems to be a safe and highly effective option for these patients with great potential to reduce side effects, and even improve clinical outcomes.”

“The combination may have worked synergistically to better fight the cancer,” Dr. Charles Simone, senior study author, told The Mesothelioma Center at Asbestos.com. “Results were impressive…with better than expected clinical outcomes.”

https://www.researchgate.net/publication/329259834_A_Novel_Prospective_Study_Assessing_the_Combination_of_Photodynamic_Therapy_and_Proton_Radiation_Therapy_Safety_and_Outcomes_When_Treating_Malignant_Pleural_Mesothelioma

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Clinical Outcomes of Patients with Recurrent Lung Cancer Reirradiated with Proton Therapy on the Proton Collaborative Group and University of Florida Proton Therapy Institute Prospective Registry Studies

Badiyan, Shahed N. et al. Practical Radiation Oncology

This is the largest series to date of Proton Beam Therapy reirradiation for recurrent lung cancer, showing that reirradiation with Proton Beam Therapy is well tolerated with acceptable toxicity and encouraging efficacy.

https://www.sciencedirect.com/science/article/pii/S1879850019300566

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