Prostate cancer (pca) is the most common non-dermatologic cancer and the 3rd leading cause of male cancer mortality in Canada. In patients with high-risk localized or recurrent pca, management ...typically includes the combination of long-term androgen deprivation therapy (adt) and radiotherapy (rt). New androgen-receptor-axis targeted therapies (arats), which await validation, offer an option to intensify therapy.
In this narrative review, we report the relevant history that has supported combining adt with rt. The literature in PubMed was searched for studies involving pca and novel arats (abiraterone acetate, enzalutamide, apalutamide, darolutamide) published between 1995 and 2019. Literature discussing clinical trials in which those modalities were combined was extracted and synthesized into a combined molecular and clinical discussion. Potential treatment intensification mechanisms and rationales are explored.
Early results from three phase i/ii trials demonstrated that concurrent abiraterone acetate, adt, and rt is safe, improves the extent of chemical castration, and is associated with limited treatment failures. A single
study implies synergy for radiosensitization beyond that facilitated by conventional adt. Studies investigating the combination of other arats with rt are under way, including multiple phase iii trials, but short-term results are not yet available.
Radiotherapy (rt) plays an important role in the treatment of lung cancer. One of the most common comorbidities in patients with lung cancer is pulmonary emphysema. The literature offers conflicting ...data about whether emphysema increases the occurrence and severity of radiation pneumonitis (rp). As a result, whether high doses of rt (with curative intent) should be avoided in patients with emphysema is still unclear.
We measured the documented incidence of rp in patients with and without emphysema who received curative radiation treatment.
This retrospective cohort study considered patients in the lung cancer clinical database of the Peter Brojde Lung Cancer Centre. Data from the database has been used previously for research studies, including a recent publication about emphysema grading, based on the percentage of lung occupied by emphysema on computed tomography (ct) imaging.
Using previously published methods, chest ct imaging for 498 patients with lung cancer was scored for the presence of emphysema. The analysis considered 114 patients who received at least 30 Gy radiation. Of those 114 patients, 64 (56%) had emphysema, with approximately 23% having severe or very severe disease. The incidence of rp was 34.4% in patients with emphysema (
= 22) and 32.0% in patients with no emphysema (
= 16,
= 0.48). No difference in the incidence of rp was evident between patients with various grades of emphysema (
= 0.96). Similarly, no difference in the incidence of rp was evident between the two treatment protocols-that is, definitive rt 17 (37%) and combined chemotherapy-rt 21 (31%,
= 0.5).
In our cohort, the presence of emphysema on chest ct imaging was not associated with an increased risk of rp. That finding suggests that patients with lung cancer and emphysema should be offered rt when clinically indicated. However, further prospective studies will be needed for confirmation.
During routine staging work-up for a left breast mass, a 68-year-old woman complained of dysphagia and dysphonia. During further investigations, a left-sided lesion at the foramen magnum was observed ...on brain imaging. Both lesions were biopsied and showed a classical chordoma.
The skull-base lesion and the breast lesion were surgically resected, and adjuvant radiotherapy was given.
Chordoma is a rare primary central nervous system tumour that seldom metastasizes. The lung is the most common site of metastasis. Synchronous breast metastasis from a skull-base chordoma is very rare, and a safe management option includes a maximum resection followed by adjuvant radiotherapy.
The use of bevacizumab in the management of glioblastoma multiforme (gbm) remains controversial. In Canada, bevacizumab is approved for the treatment of recurrent gbm. We describe a pattern of ...progression across treatment lines in gbm.
During 2008-2014, 64 patients diagnosed with gbm were treated with bevacizumab at McGill University hospitals. Of those patients, 30 (46.9%) received bevacizumab in the first line (B1L), and 34 (53.1%) received it in the second line and beyond (B2L+). The average length of treatment with bevacizumab was 24.4 weeks (range: 0-232.7 weeks). The patterns of progression were categorized as local, distant, diffuse, multifocal, or multi-pattern.
Local progression was seen in 46.7% of B1L patients and 26.5% of B2L+ patients, distant in 3.3% and 2.9%, diffuse in 20% and 47%, multifocal in 10% and 8.8%, and multi-pattern in 3.3% and 11.8%. No differences between the groups were observed for the distant (
= 0.3) or diffuse (
= 0.4) patterns. Grades 3 and 4 adverse events in the B1L and B2L+ groups were fatigue (33.3% vs. 17.6% respectively), hypertension (26.7% vs. 5.9%), thrombocytopenia (26.7% vs. 11.8%), neutropenia (26.7% vs. 11.8%), anemia (23.3% vs. 11.8%), leucopenia (20% vs. 8.8%), deep vein thrombosis (23.3% vs. 5.9%), seizure (16.7% vs. 8.8%), brain hemorrhage (6.7% vs. <1%), and delayed wound healing (6.7% vs. 2.9%). More total grades 3 and 4 adverse events occurred in the B1L group (
= 0.000519).
In our cohort, patterns of progression were not different in B1L and B2L+ patients. Moreover, both groups experienced similar adverse events, although more grades 3 and 4 events occurred in the B1L group, implying that severe adverse events in B1L patients could negatively affect survival outcomes.
Repair of radiation-induced dna double-strand breaks is a key mechanism in cancer cell radio-resistance. The synthesized compound NU7026 specifically inhibits dna-dependent protein kinase (dna-pk) ...within the non-homologous end-joining repair mechanism. Earlier studies demonstrated increased radiosensitivity in dna-pk deficient cells compared with wild-type cells. In chronic leukemia cells, NU7026 appears to enhance the cytotoxic effect of chlorambucil. The radio-modifying effects of NU7026 on cell survival, cell cycle, apoptosis, and dna double-strand break repair have yet to be studied in gastric cancer cells.
The gastric cancer cell line N87 was treated with 0 Gy or 4 Gy in the presence of NU7026 at a dose range of 0-20 μmol/L. Clonogenic assays were used to assess cell survival after treatment. Cell-cycle distribution was analyzed using propidium iodide with fluorescence-activated cell sorting. Apoptosis was detected using annexin-V and propidium iodide with fluorescence-activated cell sorting. The γH2AX assay was used to measure dna double-strand breaks.
Statistically significant increases in G2/M arrest were observed in N87 cells treated with radiation and NU7026 compared with those treated with radiation alone (p = 0.0004). Combined treatment also led to an increase in apoptosis (p = 0.01). At 24 hours, the γH2AX analysis revealed more dna double-strand breaks in N87 cells treated with radiation and NU7026 than in those treated with radiation alone (p = 0.04). Clonogenic assays demonstrated declining cell survival as both the radiation and the NU7026 dose increased. The dose enhancement factor at 0.1 survival fraction was 1.28 when N87 cells were treated with 4 Gy radiation and 5 μmol/L NU7026.
In gastric cancer cells, NU7026 appears to enhance the cytotoxic effect of irradiation as assessed by clonogenic assays. This increased cytotoxicity might be the result of an increase in dna double-strand breaks resulting in G2/M cell arrest and possibly higher levels of apoptosis.
Breast or chest-wall pain (BCP) is prevalent in 20%-50% of breast cancer survivors, and it affects quality of life (QOL). To determine the feasibility and potential efficacy of an exercise program to ...improve patient QOL and BCP, such a program was offered to breast cancer patients suffering from BCP.
The study enrolled 10 breast cancer patients with moderate-to-severe BCP at 3-6 months after completion of all adjuvant treatments. These patients participated in a 12-week comprehensive health improvement program (CHIP). Intensity was adjusted to reach 65%-85% of the patient's maximal heart rate. Before the CHIP and at 1 and 6 months after completion of the CHIP, QOL and pain were measured using questionnaires European Organisation for Research and Treatment of Cancer Quality of Life core and breast cancer modules (QLQ-C30, -BR23) and the McGill Pain Questionnaire short form completed by the patients. Results were compared with those from case-matched control subjects from another study at McGill University.
After the CHIP, patients reported significant and clinically important improvements in QOL and symptoms. At 1 and 6 months post-CHIP, patients in the study felt, on average, better in overall QOL than did historical control subjects.
Our study suggests that patients who experience chronic bcp may benefit from an exercise program. A randomized controlled trial is warranted.
Radiation-induced dermatitis is a common side effect of breast irradiation, with hypofractionation being a well-known risk factor. In the context of the widespread adoption of hypofractionated breast ...radiotherapy, we evaluated the effect of hypofractionated radiotherapy on the incidence of skin toxicity in patients receiving adjuvant chemotherapy.
We retrospectively reviewed the records of patients with breast cancer treated from 2004 to 2006 at a single institution. Patients undergoing lumpectomy with or without adjuvant chemotherapy followed by hypofractionated radiotherapy consisting of 42.4 Gy in 16 fractions were included in the study. Using cosmetic and skin toxicity scales, all patients were evaluated weekly during treatment and at scheduled follow-up visits with the radiation oncologist.
During the study period, 162 patients underwent radiotherapy, and 30% of those (n = 48) received chemotherapy. Radiotherapy boost to the tumour bed was more common in the chemotherapy group n = 20 (42%) than in the radiotherapy-alone group n = 30 (26%). We observed no statistically significant difference between the groups with regard to acute skin toxicity of grade 3 or higher (2.1% in the chemotherapy group vs. 4.4% in the radiation-alone group, p = 0.67) or of grades 1-2 toxicity (62.5% vs. 51.7% respectively, p = 0.23). There was also no significant difference in late grade 3 or higher skin toxicity between the groups (2.1% vs. 0% respectively, p = 0.30) or in grades 1-2 toxicity (20.8% vs. 25.5% respectively, p = 0.69). Similarly, excellent or good cosmetic result scores were similar in both groups (p = 0.80)
In our single-institution review, we observed no adverse effects of chemotherapy in combination with hypofractionated whole-breast irradiation. Further investigations are necessary to better elucidate the effects of chemotherapy on skin toxicity in the context of hypofractionated irradiation.
PDF
