For many patients with localised lung cancer (non-small-cell lung carcinoma and small cell lung carcinoma), high-dose radiation with concurrent chemotherapy is a potential cure.
Yet this treatment can cause severe, acute inflammation of the oesophagus (oesophagitis) in about one in five patients, requiring hospitalisation and placement of a feeding tube.
A team of radiation oncologists at Mass General Cancer Center demonstrate in an early clinical trial that the radiation beam can be carefully "sculpted" to deliver the majority of a radiation dose directly to the tumour while effectively sparing tissues in the side of the oesophagus away from the affected lung (the contralateral oesophagus), thereby limiting inflammation and preserving swallowing function.
The researchers describe their contralateral oesophagus sparing technique (CEST) in a study published in JAMA Oncology.
"Severe grade 3 oesophagitis is a terrible complication of radiation and chemotherapy," says co-senior author Henning Willers, MD, director of the Thoracic Radiation Oncology Program at Mass General Cancer Center.
"It happens 5% to 10% of the time in patients with non-small-cell lung cancer, and 15% to 20% of the time in patients with small-cell lung cancer.
Even grade 2 oesophagitis, one step lower in severity, can be tough, with patients requiring narcotics for many weeks to cope with the pain," he says.
Starting in 2013, Willers and colleagues carefully observed outcomes with various treatment techniques, including radiation methods used to treat head and neck and prostate cancers, and using a method of radiation delivery called intensity-modulated radiation therapy (IMRT) they devised CEST.
The technique involves imaging the oesophagus and then shaping a high-dose radiation beam so that the maximal amount of radiation energy is delivered to the tumour, with a steep dropoff in energy across the oesophagus, thereby sparing as much as possible the normal tissues and function in the side of the oesophagus farthest away from the treatment site.
In their initial clinical experience, investigators saw that among patients with locally advanced lung cancers who were treated with CEST and chemotherapy, none had grade 3 or greater oesophagitis, and only about 20% had grade 2 oesophagitis, which was relatively mild, even though these patients had received high doses of radiation.
"In 2014, when I was a radiation oncology resident, I noticed that patients did well with our use of this sparing technique, and with Christine C. Olsen, MD, co-principal investigator of the trial, we moved to test this concept on a formal clinical study," says lead author Sophia C. Kamran, MD, now a staff radiation oncologist at the Cancer Center.
To better determine the frequency of oesophagitis in patients treated with CEST, the investigators designed a phase 1 trial with 27 patients, 25 of whom completed combined chemotherapy and radiation. Of this group, ranging from 51 to 81 years of age, 19 had non-small-cell lung cancer, and 6 had small-cell lung cancer.
None of the 25 patients who completed chemoradiation developed grade 3o esophagitis, while 7 experienced grade 2 oesophagitis.
Other treatment side effects were within the range of what can be expected for this type of cancer. Two-thirds of patients remained alive at two years after chemoradiation, and none had an isolated local tumour recurrence.
"Our findings support emerging national guidelines, which are increasingly recognising the importance of sparing the oesophagus, although an effective method to do so has neither been formalised nor well defined until now.
This is the first prospective trial reporting on the use of a formalised technique," says Kamran.
Source: Massachusetts General Hospital