Proton Beam Therapy vs Intensity-Modulated Radiation Therapy for Locally Advanced Oesophageal Cancer

Radiation therapy has become an important component in the curative management of oesophageal cancer worldwide. Since most of the oesophageal cancers seen in the Western hemisphere (i.e., Europe and the United States) are located in the mid- to distal-oesophageal locations, heart and lungs invariably receive significant radiation doses. Much of the normal tissue exposure could be reduced with the utilisation of advanced radiation technologies such as intensity modulated proton therapy. Proton beam therapy (PBT) provides the ability to reduce normal tissue exposure (compared to conventional treatments) due to its lack of exit dose, which enables medical teams to provide clinically meaningful benefits to oesophageal cancer patients.

A Randomized Trial of Proton Beam Therapy Versus Intensity-Modulated Radiation Therapy for Locally Advanced oesophageal Cancer found that proton beam therapy was associated with less toxicity and similar progression-free survival vs intensity-modulated radiation therapy in patients with locally advanced oesophageal cancer.

In the trial, 145 patients were randomly assigned to proton beam therapy or intensity-modulated radiation therapy. Median follow-up was 44.1 months. The posterior mean total toxicity burden was 2.3 times higher in the intensity-modulated radiation therapy group vs the proton beam therapy group. The mean postoperative complication score was 7.6 times higher in the intensity-modulated radiation therapy group vs the proton beam therapy group (2.5, 95% highest posterior density interval = 0.3–5.2). At 3 years, overall survival was 51.2% vs 50.8% and median overall survival was 42.1 months vs 73.6 months.

The investigators concluded: “For locally advanced oesophageal cancer, proton beam therapy reduced the risk and severity of adverse events compared with intensity-modulated radiation therapy while maintaining similar progression-free survival.”

Treating oesophageal cancer with an adequate dose of radiation can be difficult because of the close proximity of the oesophagus to critical structures, such as the heart, lungs and spinal cord. Because protons deposit their highest dose of radiation at the tumor or area of concern, proton therapy can be an excellent choice for treating patients with oesophageal cancer.

Proton therapy offers patients and their doctors a unique option for effectively treating oesophageal cancer while reducing damage to other critical organs and tissues. The Prague Proton Therapy Center is one of the few centres of its kind treating oesophageal cancer with proton technology.

Latest proton therapy study shows hypofractionated proton therapy as safe and effective for patients with low-risk prostate cancer

A study published in August 2019 in the International Journal of Particle Therapy by Dr. Slater and his team, highlights the results of their latest phase I/II hypofractionated proton therapy study at Loma Linda University Hospital.

Prostate cancer is the most commonly diagnosed cancer in men, and many of these patients have low-risk, early disease. Prostate cancer at these stages remains highly treatable with local control rates over 90% and very low rates of late morbidity commonly reported for a variety of treatment modalities. The focus then turns to the avoidance of unnecessary negative treatment-related side effects that can occur, particularly through the use of conventional treatments such as surgery and x-ray (conventional) radiotherapy.

Proton radiation therapy has demonstrated itself to be an excellent option for low-risk prostate cancer as it delivers high control rates with very little toxicity. Proton beam thereby enhances the physician’s opportunity to minimise risks for the patient.

Hypofractionation is the process of delivering higher doses of radiation per fraction, but using fewer daily fractions. Doctors and physicists at Loma Linda University have successfully used hypofractionated proton therapy for several diseases, including cancers of the breast, lung, and liver. In each instance, control and survival rates have been maintained and unwelcome side effects have not increased. This experience prompted the medical team at Loma Linda to investigate hypofractionation for prostate cancer.

The purpose of the study was to determine whether a hypofractionated proton radiotherapy regimen can control early-stage prostate cancer while maintaining low rates of side effects similar to results obtained using standard-fraction proton radiotherapy.

A cohort of 146 patients with low-risk prostate cancer (Gleason score 7, prostate-specific antigen 10, tumor stage of T1–T2a) received 20 fractions of proton therapy (3.0 Gy per fraction over 4 weeks). Patients were evaluated at least weekly during treatment, at which time documentation of treatment tolerance and acute reactions was obtained. Follow-up visits were conducted every 3 months for the first 1 years, every 6 months for the next 3 years, then annually. Follow-up visits consisted of history and physical examination, PSA measurements, and evaluation of toxicity.

The 3-year biochemical progression-free survival rate was 99.3%, and the 5-year biochemical progression-free survival was 97.9%.

In conclusion, this study showed that hypofractionated proton therapy (60 Gy in 20 fractions) was safe and effective for patients with low-risk prostate cancer. A prospective multi-institutional randomised study is currently being conducted to confirm these results.

Sources:

Kil WJ, Nichols RC Jr, Hoppe BS, Morris CG, Marcus RB Jr, Mendenhall W, Mendenhall NP, Li Z, Costa JA, Williams CR, Henderson RH. Hypofractionated passively scattered proton radiotherapy for low- and intermediate-risk prostate cancer is not associated with post-treatment testosterone suppression. Acta Oncol. 2013;52:492–7

Mendenhall NP, Hoppe BS, Nichols RC, Mendenhall WM, Morris CG, Li Z, Su Z, Williams CR, Costa J, Henderson RH. Five-year outcomes from 3 prospective trials of image-guided proton therapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2014;88:596–602

Mendenhall NP, Li Z, Hoppe BS, Marcus RB Jr, Mendenhall WM, Nichols RC, Morris CG, Williams CR, Costa J, Henderson R. Early outcomes from three prospective trials of image-guided proton therapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2012;82:213–21

Shipley WU, Verhey LJ, Munzenrider JE, Suit HD, Urie MM, McManus PL, Young RH, Shipley JW, Zietman AL, Biggs PJ, Heney NM, Goitein M. Advanced prostate cancer: the results of a randomized comparative trial of high dose irradiation boosting with conformal protons compared with conventional dose irradiation using photons alone. Int J Radiat Oncol Biol Phys. 1995;32:3–12

Slater JD, Rossi CJ Jr, Yonemoto LT, Bush DA, Jabola BR, Levy RP, Grove RI, Preston W, Slater JM. Proton therapy for prostate cancer: the initial Loma Linda University experience. Int J Radiat Oncol Biol Phys. 2004;59:348–52

Slater JD, Rossi CJ Jr, Yonemoto LT, Reyes-Molyneux NJ, Bush DA, Antoine JE, Miller DW, Teichman SL, Slater JM. Conformal proton therapy for early-stage prostate cancer. Urology. 1999;53:978–84

Slater JD, Yonemoto LT, Rossi CJ Jr, Reyes-Molyneux NJ, Bush DA, Antoine JE, Loredo LN, Schulte RW, Teichman SL, Slater JM. Conformal proton therapy for prostate carcinoma. Int J Radiat Oncol Biol Phys. 1998;42:299–304

Slater JM, Slater JD, Kang JI, et al. Hypofractionated Proton Therapy in Early Prostate Cancer: Results of a Phase I/II Trial at Loma Linda University. Int J Part Ther. 2019;6(1):1–9. doi:10.14338/IJPT-19-00057

Zietman AL, Bae K, Slater JD, Shipley WU, Efstathiou JA, Coen JJ, Bush DA, Lunt M, Spiegel DY, Skowronski R, Jabola BR, Rossi CJ. Randomized trial comparing conventional-dose with high-dose conformal radiation therapy in early-stage adenocarcinoma of the prostate: long-term results from Proton Radiation Oncology Group/American College of Radiology 95-09. J Clin Oncol. 2010;28:1106–11

New study shows proton therapy more effective than conventional radiotherapy in the treatment of intrahepatic cholangiocarcinoma (ICC)

In a recent study by the Massachusetts General Hospital Department of Radiation Oncology, the use of proton therapy for intrahepatic cholangiocarcinoma (ICC) was shown to more effectively control the cancer and improve the chances of survival – particularly in comparison to conventional (photon) radiotherapy.

Cholangiocarcinoma is a cancer that develops in the cells within the bile ducts; both inside and outside the liver. The terms cholangiocarinoma and bile duct cancer are often used to refer to the same condition. This condition occurs slightly more often in males than females and usually affects people who are between 50-70 years old. Signs and symptoms of intrahepatic cholangiocarcinoma include jaundice, abdominal pain, fever, weight loss, weakness and itching. Treatment options may include surgery (when possible) to remove the bile duct and parts of the liver, chemotherapy and radiation.

In certain cases cholangiocarcinoma is an unresectable form of cancer. Unresectable cancer is defined as a cancer or tumour that cannot be removed completely through surgery. In these cases, radiotherapy and chemotherapy offer the best chances of survival.

The aim of this study was to evaluate outcomes for patients with unresectable intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated proton or photon radiation therapy.

66 patients with unresectable intrahepatic cholangiocarcinoma were treated with hypofractionated proton (32 patients) or photon (34 patients) radiation therapy. Median radiotherapy (RT) dose was 58.05 Gy, all delivered in 15 daily fractions. On multivariate analysis for overall survival (OS), compared with photon RT, there was a trend towards improved survival with proton RT (HR 0.50; p = 0.05).

Median follow-up times from diagnosis and RT start were 21 months and 14 months, respectively. In total, five patients (7.6%) developed local failure. The 2-year outcomes were 84% local control (LC) and 58% OS. Among the 51 patients treated with definitive intent, the 2-year LC rate was 93% and the OS rate was 62%.

The study concluded that hypofractionated radiation therapy yields high rates of local control and is an effective modality to optimize biliary control for unresectable/locally recurrent ICC.

At the ESMO World Congress on Gastrointestinal Cancer 2019, it was identified that high dose radiotherapy in unresectable ICC should be considered as a viable treatment option, in combination with systemic therapy.

This study adds to the growing body of evidence suggesting proton beam therapy as a safe and effective treatment for patients with unresectable ICC. It is proposed therefore, that – pending further research – proton therapy be utilised as a curative treatment for ICC.

Sources:

Hong TS, Wo JY, Yeap BY, Ben-Josef E, McDonnell EI, Blaszkowsky LS, Kwak EL, Allen JN, Clark JW, Goyal L, et al. Multi-institutional phase II study of high-dose Hypofractionated proton beam therapy in patients with localized, Unresectable hepatocellular carcinoma and intrahepatic Cholangiocarcinoma. J Clin Oncol. 2016;34(5):460–8

Ohkawa A, Mizumoto M, Ishikawa H, Abei M, Fukuda K, Hashimoto T, Sakae T, Tsuboi K, Okumura T, Sakurai H. Proton beam therapy for unresectable intrahepatic cholangiocarcinoma. J Gastroenterol Hepatol. 2015;30(5):957–63

Shimizu, S., Okumura, T., Oshiro, Y. et al. Clinical outcomes of previously untreated patients with unresectable intrahepatic cholangiocarcinoma following proton beam therapy. Radiat Oncol 14, 241 (2019)

Smart AC, Goyal L, Horick N, Petkovska N, Zhu AX, Ferrone CR, Tanabe KK, Allen JN, Drapek LC, Qadan M, Murphy JE, Eyler CE, Ryan DP, Hong TS, Wo JY. Hypofractionated Radiation Therapy for Unresectable/Locally Recurrent Intrahepatic Cholangiocarcinoma. Ann Surg Oncol. 2019 Dec 23. doi: 10.1245/s10434-019-08142-9 [Epub ahead of print]

Ustundag Y, Bayraktar Y. Cholangiocarcinoma: a compact review of the literature. World J Gastroenterol. 2008;14(42):6458–66

Superior Intellectual Outcomes After Proton Radiotherapy Compared With Photon Radiotherapy for Pediatric Medulloblastoma

Proton Radiotherapy Preserves Intellectual Function in Children suffering from Medulloblastoma – New study shows that children treated with Proton Therapy have superior intellectual outcomes, compared to children treated with conventional photon/x-ray radiotherapy.

Radiotherapy is essential for treating children’s brain tumours – however conventional radiotherapy treatment increases the risk of permanent cognitive impairment. Memory problems, learning problems, global IQ decline, and other serious cognitive impairments can occur. A new study published in the Journal of Clinical Oncology on the 27th November 2019 has demonstrated the superiority of proton therapy over traditional x-ray/photon radiotherapy in treating paediatric Medulloblastoma.

Medulloblastoma is an invasive, rapidly growing form of tumour, and the most commonly occurring type of brain cancer in children. This study showed that the use of proton therapy in treating these cancers (instead of conventional photon/x-ray radiotherapy) resulted in significantly improved long-term intelligence outcomes in children.

This study provides the strongest evidence to date that proton therapy preserves the intellectual function of children with medulloblastoma – as opposed to traditional x-ray radiation which can cause damage and result in a lower quality of life for children following treatment. The authors of the study concluded:

“Even in the context of CSI (craniospinal irradiation), patients treated with PRT (Proton RadioTherapy) exhibited stable intellectual outcomes in most domains and experienced significantly better long-term outcomes in global IQ, perceptual reasoning, and working memory compared with patients treated with XRT (conventional x-ray radiotherapy).”

These results expand on previous research suggesting an intellect-sparing benefit of proton therapy in the treatment of paediatric brain tumors, reported Lisa S. Kahalley, PhD, of Texas Children’s Hospital (TCH) in Houston, and colleagues in the Journal of Clinical Oncology.

“It’s getting very difficult to argue that there isn’t a very strong clinical benefit associated with proton, so now it really becomes an access issue. We have to think really hard about ways to improve access to families that aren’t located near proton centres.”

The Proton Therapy Center in Prague has considerable experience treating children’s brain tumours with protons, and has treated many children suffering from medulloblastoma – including British child Ashya King, who received proton therapy at the Prague Proton Therapy Center after an international manhunt in 2014. Ashya’s story received widespread public attention, and his successful proton therapy treatment in Prague resulted in him having less risk of cognitive problems following treatment.

Extreme hypofractionated proton radiotherapy for prostate cancer using pencil beam scanning: Dosimetry, acute toxicity and preliminary results

Prague Proton Therapy Medical Team Publishes their Latest Results, Using Proton Therapy to Treat Prostate Cancer.

Several treatment options exist for managing prostate cancer in men. Surgery and conventional radiotherapy have been shown to be equally effective at treating prostate cancer, however conventional treatments such as these can result in side effects that can reduce overall quality of life. Proton therapy is equally effective at treating prostate cancer, however causes less side effects, thereby preserving the quality of life of patients during and after treatment.

Proton therapy has been used to treat prostate cancer for over 25 years. Doctors at the Proton Therapy Center (PTC) in Prague have been treating prostate cancer with proton therapy since opening their facility in 2012. The Prague Proton Therapy Center uses the most advanced form of proton therapy available known as ‘Intensity-Modulated Proton Therapy’ (IMPT) – otherwise known as ‘Pencil-Beam Scanning’ (PBS). This highly accurate form of proton therapy allows high doses of cancer-killing proton radiation to be delivered to the tumour, while sparing healthy surrounding tissue from harm.

The PTC medical team have published their latest treatment findings, using IMPT proton therapy to treat prostate cancer. Their success in treating prostate cancer with proton therapy was published in the Journal of Medical Imaging and Radiation Oncology (the Official Journal of The Royal Australian and New Zealand College of Radiologists).

This study follows the progress of 200 prostate cancer patients that received an advanced and accelerated proton treatment program. The results show that this treatment is extremely effective at treating and removing prostate cancer. The research also shows that proton therapy for prostate cancer results in extremely low side effects. The PTC medical team was able to successfully remove the prostate cancer with almost no side effects using an accelerated, 2 week treatment schedule.

Side effects to the bladder and bowel are commonly reported among patients undergoing conventional radiotherapy for prostate cancer. The Radiation Therapy Oncology Group (RTOG) rates side effects on a ‘grading’ scale from 0 (none) to 4 (severe). Patients examined during the PTC study experienced an extremely low degree of bladder side effects, or in many cases, no side effects at all (grade 0). Only 22.5% of patients experienced grade 2 side effects. The majority of these grade 2 side effects completely disappeared following treatment. Patients undergoing treatment experienced absolutely no severe (i.e. no grade 3 or 4) bladder-related side effects.

In addition to low bladder-related side effects, patients undergoing proton therapy in Prague experienced virtually no bowel side effects. 20% of patients experienced mild, short-term bowel-related side effects that disappeared following treatment. Importantly, 80% of patients experienced no bowel-related side effects during or after treatment. Excitingly, no patients experienced severe (grade 3 or 4) side effects!

To read more about their latest results using proton therapy for prostate cancer, click here.

Comparative Effectiveness of Proton vs Photon Therapy as Part of Concurrent Chemoradiotherapy for Locally Advanced Cancer

Doctors at the University of Pennsylvania in Philadelphia published retrospective, nonrandomised comparative effectiveness study that compares proton versus photon therapy for concurrent chemoradiotherapy of locally advanced cancer.

The authors compared adverse events associated with unplanned hospitalisations among 1,483 adult patients with nonmetastatic, locally advanced cancers treated with concurrent chemoradiotherapy and proton therapy (391 patients) or photon therapy (1092 patients). The results were published in August 2019 in JAMA Oncology. This study found that proton therapy significantly reduced severe adverse events in adults with locally advanced cancers without affecting outcomes when compared with photon therapy.

Concurrent chemoradiotherapy can be associated with substantial toxicity, including
oral mucositis, oesophagitis, nausea, vomiting, signifiant weight loss, and radiation-induced lung injury that can result in unplanned hospitalisations, emergency department visits,
treatment interruptions that can diminish the effectiveness of treatment, and decreased patient performance status.

Proton therapy as part of concurrent chemoradiotherapy may be able to reduce treatment toxicity, but limited data have been so far available comparing results of proton chemoradiotherapy with chemoradiotherapy delivered with photon therapy, and proton therapy remains unproven in this setting. This comparative effectiveness cohort study focused therefore on the rate of severe 90-day adverse events associated with unplanned hospitalisations.

The study comes to a result that compared with photon therapy, proton therapy was associated with a nearly two-thirds reduction in 90-day severe adverse events associated with unplanned hospitalisations. Proton therapy was also associated with significantly lower risk of a decline in Eastern Cooperative Oncology Group (ECOG) performance status and significantly less risk of adverse events causing impairment in patients’ instrumental activities of daily living.

Proton therapy was also shown to be equally effective at treating the cancer – disease-free and overall survival outcomes were similar between the two groups, which included patients with head and neck, lung, brain, oesophagus/gastric tract, rectum, and pancreas cancers.

Before this study, data on the toxicity differences between proton vs photon chemo-radiotherapy have been limited, with relatively small patient numbers, although most studies have found a toxicity advantage and/or dosimetric advantage in favour of proton chemoradiotherapy.

This study mentions 3 important implications for future research:

  • First, proton therapy’s lower observed toxicity raises the possibility that the higher up-front cost of proton therapy may be offset by cost savings from reduced hospitalisations  and enhanced productivity from patients and caregivers.
  • Second, the lower observed toxicity of proton therapy offers an opportunity to explore clinical trials combining proton therapy with intensified systemic therapy and/or dose-escalated radiotherapy, which may, in turn, improve survival outcomes.
  • Third, proton therapy may allow also older, sicker patients with more comorbidities to receive the most effective combined-modality treatments.