Surgery May Not Be Needed With Locally Advanced Rectal Cancer

A short course of radiation therapy followed by neoadjuvant chemotherapy resulted in a clinical complete response (CR) in almost half of 90 patients with locally advanced rectal cancer, allowing the majority of responders to skip surgical resection, a retrospective study indicates.

Specifically, at a median follow-up of 16.6 months for living patients, the initial clinical CR was 48% overall.

“While we do not have enough follow-up yet to know the late side-effect profile of this regimen, our preliminary results are promising,” Re-I. Chin, MD, Washington University School of Medicine, St. Louis, Missouri, told Medscape Medical News in an email.

The study was presented at the virtual 2020 meeting of the American Society of Radiation Oncology (ASTRO).

“Certainly longer follow-up will be needed in this study but none of the observed patients to date has experienced an unsalvageable failure,” said meeting discussant Amol Narang, MD, of Johns Hopkins University, Baltimore, Maryland.

He reminded conference attendees that despite good evidence supporting equivalency in oncologic outcomes between short-course radiation and long-course chemoradiation, the former is “highly underutilized in the US” with a mere 1% usage rate between 2004 and 2014.

The current study’s short-course treatment approach was compared in this setting to long-course chemoradiation and adjuvant chemotherapy in the  RAPIDO trial reported at the 2020 annual meeting of the American Society of Clinical Oncology (ASCO), Narang pointed out.

Short-course patients had a higher rate of pathological complete response (pCR) and a lower rate of treatment failure compared with patients who received long course chemoradiation and adjuvant chemotherapy; both patient groups underwent total mesorectal excision — which is different from the current analysis. The RAPIDO investigators concluded that the approach featuring the short-course “can be considered as a new standard of care.”

Narang said the data collectively “begs the question as to whether the superiority of long course chemoradiation should really have to be demonstrated to justify its use.”

But Chin highlighted toxicity issues. “Historically, there have been concerns regarding toxicity with short-course radiation therapy since it requires larger doses of radiation given over a shorter period of time,” Chin explained. “But [the short course] is particularly convenient for patients since it saves them more than a month of daily trips to the radiation oncology department.”

Seven Local Failures

The single-center study involved patients with newly diagnosed, nonmetastatic rectal adenocarcinoma treated with short course radiation therapy followed by chemotherapy in 2018 and 2019. Nearly all (96%) had locally advanced disease, with either a T3/T4 tumor or node-positive disease.  Median tumor size was 4.6 cm.

“Many of the patients in the study had low lying tumors,” Chin reported, with a median distance from the anal verge of 7 cm.

Radiation therapy was delivered in 25 Gy given in five fractions over 5 consecutive days, with the option to boost the dose to 30 Gy or 35 Gy in five fractions if extra-mesorectal lymph nodes were involved. Conventional 3D or intensity-modulated radiation was used and all patients completed treatment.

The median interval between diagnosis of rectal

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The most advanced Covid-19 vaccine trials won’t tell us if the shots save lives, expert notes

The most advanced trials for coronavirus vaccines cannot tell researchers if the shots will save lives, or even if they’ll prevent serious disease, a drug development expert pointed out Wednesday.

a woman smiling for the camera

© Reuters / University of Oxford

The ongoing trials are only designed to show if the vaccines prevent infection — and most infections are mild infections, Peter Doshi, an associate editor at the BMJ medical journal and a drug development specialist at the University of Maryland’s school of pharmacy, said.

“I think there are some pretty widely held assumptions about what we are getting out of Phase 3 studies,” Doshi told CNN.

“None of the trials currently under way are designed to detect a reduction in any serious outcome such as hospital admissions, use of intensive care, or deaths. Nor are the vaccines being studied to determine whether they can interrupt transmission of the virus,” Doshi wrote in the BMJ.

“Hospital admissions and deaths from Covid-19 are simply too uncommon in the population being studied for an effective vaccine to demonstrate statistically significant differences in a trial of 30,000 people. The same is true of its ability to save lives or prevent transmission: the trials are not designed to find out.”

Four vaccines being developed in the US are in the most advanced, Phase 3 stage of development: those being made by Moderna, Pfizer, AstraZeneca and Johnson & Johnson. They’re “event-driven” trials, meaning that the goal is to keep them going until a certain number of volunteers become infected. If more infections are seen among people who got placebo, or dummy shots, it’s an indication the vaccines prevented infection.

But that doesn’t mean the vaccines saved people from serious disease or death, Doshi argued.

“Severe illness requiring hospital admission, which happens in only a small fraction of symptomatic Covid-19 cases, would be unlikely to occur in significant numbers in trials,” he wrote.

The US Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee meets Thursday to discuss the ongoing coronavirus vaccine trials and what members would like the FDA to consider when reviewing any applications for either emergency use authorization for a vaccine, or full approval.

Doshi said they should consider asking the companies to reconfigure their trials to include data on preventing severe illness and death.

“People expect that the most severe part of the Covid iceberg — the ICU admissions and hospitalizations and deaths — that’s what a vaccine would put an end to,” he said.

But the current trials will just look for early infections. It’s possible to keep these current trials going and add onto them so that they will, eventually, answer the question of whether Covid vaccines save lives and prevent severe disease.

“The trials are ongoing,” he told CNN. “There’s a chance for that. It’s not too late.”

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