Could radiotherapy do more harm than good in some patients?
2015 Study abstract
Treatment with ionizing radiation (IR) can lead to the accumulation of tumor-infiltrating regulatory T cells (Treg cells) and subsequent resistance of tumors to radiotherapy. Here we focused on the contribution of the epidermal mononuclear phagocytes Langerhans cells (LCs) to this phenomenon because of their ability to resist depletion by high-dose IR. We found that LCs resisted apoptosis and rapidly repaired DNA damage after exposure to IR. In particular, we found that the cyclin-dependent kinase inhibitor CDKN1A (p21) was overexpressed in LCs and that Cdkn1a−/− LCs underwent apoptosis and accumulated DNA damage following IR treatment. Wild-type LCs upregulated major histocompatibility complex class II molecules, migrated to the draining lymph nodes and induced an increase in Treg cell numbers upon exposure to IR, but Cdkn1a−/− LCs did not. Our findings suggest a means for manipulating the resistance of LCs to IR to enhance the response of cutaneous tumors to radiotherapy.
Sources and more information
CDKN1A regulates Langerhans cell survival and promotes Treg cell generation upon exposure to ionizing irradiation, Nature Immunology, doi:10.1038/ni.3270, 07 September 2015.
Could radiotherapy do more harm than good in some patients?dailymail, 7 September 2015.
Doctors and researchers are constantly looking for ways to improve treatments
Treating cancers with immunotherapy and radiotherapy at the same time could stop them from becoming resistant to treatment, according to a study published in Cancer Research.
The researchers, based at The University of Manchester and funded by Cancer Research UK and MedImmune found that combining the two treatments helped the immune system hunt down and destroy cancer cells that were not killed by the initial radiotherapy in mice with breast, skin and bowel cancers.
Sources and more information:
Acquired Resistance to Fractionated Radiotherapy Can Be Overcome by Concurrent PD-L1 Blockade, Cancer Research, October 1, 2014 74;5458.
Immunotherapy could stop resistance to radiotherapy, Cancer Research UK Press release, 1 October 2014.
Breast-conserving surgery led to improved cancer-specific survival in early breast cancer as compared with mastectomy, with or without radiation therapy
Breast-conserving surgery led to improved cancer-specific survival in early breast cancer as compared with mastectomy, with or without radiation therapy, a large retrospective review showed.
Patients treated with breast conservation had significantly higher 5- and 10-year survival, including an 11% absolute difference from mastectomy plus radiation therapy at 10 years, according to researchers of the University of Utah.
Effect of Breast Conservation Therapy vs Mastectomy on Disease-Specific Survival for Early-Stage Breast Cancer, JAMA Surg. 1813803 2014;149(3):267-274. doi:10.1001/jamasurg.2013.3049.
Breast-Conserving Therapy for Triple-Negative Breast Cancer, JAMA Surg. 1793208 2014;149(3):252-258. doi:10.1001/jamasurg.2013.3037.
Breast-Conserving Therapy: A Viable Option for Young Women with Early Breast Cancer-Evidence from a Prospective Study, NCBI, PMID: 24599412, 2014 Mar 6
BACKGROUND: This study evaluated the security of breast-conserving treatment (BCT) in young patients and the effect of regional radiation therapy on young patients with 1-3 positive nodes (N+) treated with BCT. METHODS: In this prospective concurrent controlled study, 164 patients were defined as the BCT group, and regional radiation therapy was delivered to patients with 1-3 N+. Modified radical mastectomies (MRMs) were performed on 224 patients without regional radiation therapy. RESULTS: The 9-year local recurrence (LR) rate of the BCT was 7 %, compared with 3 % in the MRM group (p = 0.055). The 9-year regional recurrence (RR) rate was 6 % for the BCT group and 12 % for the MRM group (p = 0.048). The distant metastasis (DM)-free and breast cancer-specific survival rates were similar between the two groups. RR was an independent prognostic factor for DM [hazard ratio 3.27; 95 % confidence interval (CI) 1.726-6.208] and breast cancer-specific survival (hazard ratio 5.814; 95 % CI 2.690-12.568), whereas LR was not an independent prognostic factor for DM or breast cancer-specific survival. CONCLUSIONS: Young patients treated with BCT have a higher LR rate than that of MRM. However, LR has no detrimental effect on DM-free and breast cancer-specific survival rates, whereas RR is a strong risk factor of DM and death. Regional radiation therapy for young patients with 1-3 N+ may reduce RR and improve survival rates.
Lord Saatchi’s Medical Innovation Bill “the SaatchiBill” would help doctors innovate new treatments and cures for cancer and other diseases
” Lord Saatchi’s Medical Innovation Bill “the Saatchi Bill” will help doctors innovate new treatments and cures for cancer and other diseases.
The Medical Innovation Bill will save lives by supporting doctors who want to innovate and find new ways of treating disease.
Doctors, patients and judges will have much greater clarity as to what is negligent and dangerous practice by clinicians and what is careful and sensible innovation.
It will free your doctor to consider new treatments and ideas. But, and more importantly, it will allow the patient to demand innovative treatment.
One of the most famous examples of innovation is when Geoffrey Keynes, a doctor at Barts, refused to do what surgeons across the UK and US were doing with breast cancer – the Halsted method – whereby women with breast cancer faced a double mastectomy, and the removal of all tissue from the shoulder, to the chest wall, to ribs – anything and everything that could be removed without killing the women.
Keynes, alone, removed only the tumour and undertook radiotherapy, in combination. He was ridiculed and humiliated on a world stage. Halsted followers called it a ‘lumpectomy’ as a term of derision. Of course, today, the lumpectomy is standard procedure.
That was innovation.
Once passed, a patient, armed with the legislation, will be able to say to his or her doctor: ‘Are you trying everything? Can you do anything differently?’ The doctor will no longer need to say he or she cannot risk trying anything new. ”
Significant breakthrough could tackle over-diagnosis and over-treatment of breast cancer
When we talk about breast cancer this usually means tumours that grow into the surrounding breast tissue, called invasive breast cancer.
However, sometimes cancerous changes develop within the lobules or ducts of the breast and do not break out into the surrounding tissue.
Ductal Carcinoma In Situ (DCIS) refers to non-invasive cancerous changes that are contained within the ducts. Researchers believe they have identified a molecule – called αvβ6 (alpha v beta 6) – that could be key to preventing over-treatment of breast cancer by revealing which cases of DCIS are most likely to develop into early invasive breast cancer.
Around 4,800 cases of DCIS are diagnosed each year in the UK with early signs of breast cancer but until now doctors have been unable to distinguish between the cases which will become dangerous, and those which do not need treatment.
Scientists say they have made a huge step forward in developing a simple test, which could free half such women from undergoing needless surgery and gruelling sessions of radiotherapy and hormone therapy.
First results of the randomised UK FAST Trial of radiotherapy hypofractionation for treatment of early breast cancer
For the first time, researchers have estimated the daily dose of radiotherapy that could be wasted in compensating for cancer cell growth that occurs overnight and during weekends in patients with early breast cancer.
The new study suggests that shorter radiotherapy schedule may:
be more effective against breast cancer recurrence
reduce the chances of side-effects on the surrounding normal tissues
Randomised trials testing 15- or 16-fraction regimens of adjuvant radiotherapy in women with early breast cancer have reported favourable outcomes compared with standard fractionation. To evaluate hypofractionation further, two 5-fraction schedules delivering 1 fraction per week have been tested against a 25-fraction regimen.
Materials and methods
Women aged ⩾50 years with node negative early breast cancer were randomly assigned after microscopic complete tumour resection to 50 Gy in 25 fractions versus 28.5 or 30 Gy in 5 once-weekly fractions of 5.7 or 6.0 Gy, respectively, to the whole breast. The primary endpoint was 2-year change in photographic breast appearance.
Nine hundred and fifteen women were recruited from 2004 to 2007. Seven hundred and twenty-nine patients had 2-year photographic assessments. Risk ratios for mild/marked change were 1.70 (95% CI 1.26–2.29, p < 0.001) for 30 Gy and 1.15 (0.82–1.60, p = 0.489) for 28.5 Gy versus 50 Gy. Three-year rates of physician-assessed moderate/marked adverse effects in the breast were 17.3% (13.3–22.3%, p < 0.001) for 30 Gy and 11.1% (7.9–15.6%, p = 0.18) for 28.5 Gy compared with 9.5% (6.5–13.7%) after 50 Gy. With a median follow-up in survivors of 37.3 months, 2 local tumour relapses and 23 deaths have occurred.
At 3 years median follow-up, 28.5 Gy in 5 fractions is comparable to 50 Gy in 25 fractions, and significantly milder than 30 Gy in 5 fractions, in terms of adverse effects in the breast.
Can drugs shield sensitive gastrointestinal tract from toxic effects?
Scientists may have found a way of protecting cancer patients from the lethal effects of radiotherapy and chemotherapy using drugs that shield the sensitive gastrointestinal tract from the toxic effects of the treatment.