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Concurrent chemotherapy with radiation therapy did not significantly increase the cumulative incidence of second pelvic malignancies, though it did increase the cumulative incidence of second non-pelvic malignancies compared with chemotherapy alone in patients with locally advanced rectal cancer, according to results from a study shared in the International Journal of Radiation Oncology, Biology, Physics.

In the concurrent chemotherapy group, the 5- and 10-year cumulative incidences of second pelvic malignancy development was 2.1% (95% CI, 1.4%-3.0%) and 5.8% (95% CI, 4.2%-7.6%); in the chemotherapy alone group, the rates were 2.3% (95% CI, 0.92%-4.8%) and 4.2% (95% CI, 1.3%-9.8%), respectively. This difference did not reach statistical significance (Gray’s Test P = .3).

A multivariable analysis showed that older age was associated with second pelvic malignancies (MV HR, 3.03; 95% CI, 1.39-6.60; P = .005), though chemotherapy alone was not significantly associated with fewer second pelvic malignancies (MV HR, 0.66; 95% CI, 0.30-1.44; P = .3).

Intensity-modulated radiation therapy and volumetric modulated arc therapy techniques were associated with reduced risk of second pelvic malignancies vs conventional and 3D conformal radiation therapy on univariable analysis (P = .014).

The most common second pelvic malignancies were prostate adenocarcinoma (31%; n = 23) and uterine cancer (28%; n = 21); uterine cancers were mostly serous, clear cell, or endometrioid, though 5 patients in the concurrent chemotherapy group developed carcinosarcomas.

The 10-year cumulative incidence of non-pelvic second malignancies was 11.0% (95% CI, 9.1%-14.1%) in the concurrent chemotherapy group and 4.4% (95% CI, 2.2%-7.9%) in the chemotherapy alone group (Gray’s Test P = .017).

Univariable analysis showed that being older than 50 was significantly associated with increased risk of second non-pelvic malignancies (HR, 2.48; 95% CI, 1.40-4.11; P ≤.001), and being male was associated with a decreased risk (HR, 0.61; 95% CI, 0.44-0.85; P = .004). Further, diabetes was associated with a second non-pelvic cancer (HR, 1.51; 95% CI, 1.05-2.19; P = .028), and abstaining from tobacco decreased the risk of second non-pelvic cancer (HR, 0.63; 95% CI, 0.43-0.91; P = .013).

The most common second non-pelvic cancers were lung cancer (24%; n = 35), breast cancer (15%; n = 21), and hematologic malignancies (13%; n = 19). While 77% of those who developed a second non-pelvic cancer did not have a diagnosis of any other cancer, 13% did also develop a second pelvic malignancy.

Regarding radiation dosimetry and technique, 21 patients who developed a second pelvic malignancy had a chemotherapy plan available; of the 21, 9 developed uterine cancer with a mean dose of 4800cGy (range, 4296-5087).

The median overall survival (OS) in the concurrent chemotherapy group was 12 years (95% CI, 11-13) vs 24 years (95% CI, 15-unreached) in the chemotherapy alone cohort. The 5- and 10-year OS rates for those who received concurrent chemotherapy for rectal cancer was 78% (95% CI, 76%-80%) and 58% (95% CI, 55%-61%), respectively; in those who received chemotherapy alone, the rates were 88% (95% CI, 84%-91%) and 76% (95% CI, 70%-82%).

The 10-year survival for those who did not develop second pelvic malignancies was 60% (95% CI, 57%-63%) vs 77% (95% CI, 67%-87%) in those who did develop a second pelvic malignancy (P = .042).

“These data serve as a foundation for future prospective studies evaluating ways to further reduce the risk of second malignancies in high-risk patients undergoing [concurrent chemotherapy] for rectal cancer,” wrote lead study author Carla Hajj, MD, of the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center, and coauthors, in the paper. “Areas of potential investigation include personalized treatments using more modern technologies such as proton beam [radiation therapy] or MRI-based treatment deliveries, lifestyle changes, and robust survivorship programs.”

The study included 2624 patients with locally advanced rectal cancer, of whom 460 were treated with chemotherapy without radiation therapy and 2164 received concurrent chemotherapy. The most common adjuvant chemotherapy regimens were folinic acid, fluorouracil (5FU), and oxaliplatin (FOLFOX; 60%), 5FU (32%), and capecitabine/oxaliplatin (CapeOx; 4%).

Eligible patients had disease treated with chemotherapy with or without pelvic radiation therapy who were identified from an institutional database by Cancer Database, ICD-9/10, and ICD-0 histologic diagnosis codes for “rectum” or “rectosigmoid”.

Patients were ineligible for participation if they had received prior pelvic radiation therapy or if their treatment was for recurrent disease.

Second malignancies were defined as those preceding the rectal cancer diagnosis date by more than 6 months, synchronous cancers were defined as within 6 months of diagnosis, and metachronous cancers were defined as occurring between 6 months and 2 years after diagnosis. A second cancer was defined as occurring more than 2 years after diagnosis of locally advanced rectal cancer. The development of a non-pelvic cancer did not preclude capturing the diagnosis of a second pelvic cancer.

Reference

Tringale KR, Patel KH, Hilal L, et al. Development of second malignancies following chemotherapy with or without radiation therapy for the treatment of locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. Published online July 19, 2025. doi:10.1016/j.ijrobp.2025.07.1424

A long-term study suggests that cannabis-based medical treatments may bring lasting relief to people with chronic insomnia.

Over 18 months, patients reported not only better sleep but also reduced anxiety, less depression, and even lower pain levels. Side effects were mild and temporary for most, making cannabis a potential alternative where traditional sleep medications fall short.

Cannabis-Based Products Show Promise

People living with insomnia who used cannabis-based medical treatments reported sleeping better for as long as 18 months, according to research published August 27 in the open-access journal PLOS Mental Health. The study was led by Arushika Aggarwal of Imperial College London, U.K., along with her colleagues.

Sleep problems affect roughly one in three people, and about 10 percent of adults meet the criteria for an insomnia disorder. Standard treatment options are often hard to access, and medications approved for insomnia carry a risk of dependence.

To explore whether cannabis-based therapies might ease insomnia, the researchers reviewed outcomes from 124 patients who were prescribed medical cannabis. They tracked changes in reported sleep quality, anxiety and depression levels, and overall quality of life across one to 18 months of treatment.

Lasting Sleep and Mental Health Benefits

Patients consistently reported better sleep throughout the 18-month period. They also noted reduced anxiety and depression, along with lower levels of pain. Around nine percent experienced side effects such as fatigue, dry mouth, or insomnia, but none were considered serious. While more rigorous randomized controlled trials are required to confirm safety and effectiveness, the results suggest that cannabis-based medical products may provide a new avenue for improving sleep among people with chronic insomnia.

Co-author Dr. Simon Erridge, Research Director at Curaleaf Clinic, explained: “Over an 18-month period, our study showed that treatment for insomnia with cannabis-based medicinal products was associated with sustained improvements in subjective sleep quality and anxiety symptoms. These findings support the potential role of medical cannabis as a medical option where conventional treatments have proven ineffective, though further randomised trials are needed to confirm long-term efficacy.”

Importance of Long-Term Monitoring

He adds: “Conducting this long-term study provided valuable real-world evidence on patient outcomes that go beyond what we typically see in short-term trials. It was particularly interesting to observe signs of potential tolerance over time, which highlights the importance of continued monitoring and individualised treatment plans.”

Reference: “UK Medical Cannabis Registry: A clinical outcomes analysis for insomnia” by Arushika Aggarwal, Simon Erridge, Isaac Cowley, Lilia Evans, Madhur Varadpande, Evonne Clarke, Katy McLachlan, Ross Coomber, James J. Rucker, Mark W. Weatherall and Mikael H. Sodergren, 27 August 2025, PLOS Mental Health.
DOI: 10.1371/journal.pmen.0000390

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Doctors often struggle to get clear images of the inner ear, a tightly protected organ encased in bone. The body’s natural obstacles make it difficult to get magnetic resonance imaging (MRI) contrasts into the ear to diagnose tumors, infections, or malformations. Now a team of researchers has developed a nanoparticle-based MRI contrast that can grab on to inner ear cells and sneak its way inside (Chem. Biomed. Imaging 2025, DOI: 10.1021/cbmi.5c00049).

“Standard . . . imaging agents rarely reach this tissue and clear out very fast, forcing clinicians to use higher doses, which raises the risk of hearing damage and toxicity,” says Huan Wang, a biomedical chemist at Changchun Institute of Applied Chemistry and the study’s senior author. The challenge comes from a protective set of cells lining the blood vessels between the middle and inner labyrinth of the ear—the blood-labyrinth barrier, or BLB.

This cellular defense allows nutrients and oxygen to pass through but blocks other molecules, including many drugs and contrast agents. To address this, Wang’s team has created the first guided MRI nanoprobe shown to cross this BLB and accumulate in the inner ear.

The probe combines three features: an iron oxide core just 3.3 nm across that serves as the MRI contrast, a polyethylene glycol (PEG) coating that keeps the contrast circulating in the bloodstream, and a short peptide intermingled with the PEG called IETP2.

Wang explains that the IETP2 sticks to LRP1—a receptor found throughout the body but especially abundant in the BLB—which is able to ferry useful molecules across the barrier, essentially letting the nanoprobe hitch a ride into the inner ear. “By attaching the nanoparticles to a peptide which targets the receptor on the BLB, the team found a way to push the probes past the barrier,” says Carmen Burtea, a biomedical imaging researcher at Université de Mons who was not involved in the study.

In mice, the nanoprobes crossed the BLB efficiently and stayed in circulation long enough to reach the cochlea. They produced up to 84% stronger MRI signals than untargeted controls, with no damage to any major organs.

“The untargeted version of the nanoprobe is already known to enhance contrast at lower doses than [standard] gadolinium agents,” Burtea says. She adds that if the probe passes risk assessments, it could give doctors a new tool to diagnose both fluid buildup and structural changes within the inner ear.

Wang agrees that clinical translation will require toxicology tests and larger-animal studies. Johannes Gerb, a biomedical imaging researcher at Ludwig Maximilian University Munich who also was not involved in the study, notes that if the probe can match gadolinium’s performance at lower cost and with comparable safety in humans, “it could become a viable alternative.”

Looking ahead, Wang says that “the platform can also be used as a general platform to ferry drugs or gene therapies to the inner ear,” though he cautions that avoiding unintended delivery to other LRP1-expressing tissues would require troubleshooting. The potential also resonates with clinicians. “Modalities such as this are an exciting avenue as they can definitely reduce the toxic loads of current medications,” says Rajesh Bhardwaj, an otolaryngologist at MedFirst ENT Centre in India who was not involved in the study.