Multivariable prognostic modelling to improve prediction of colorectal cancer recurrence: the PROSPeCT trial.

OBJECTIVE: Improving prognostication to direct personalised therapy remains an unmet need. This study prospectively investigated promising CT, genetic, and immunohistochemical markers to improve the prediction of colorectal cancer recurrence. MATERIAL AND METHODS: This multicentre trial (ISRCTN 95037515) recruited patients with primary colorectal cancer undergoing CT staging from 13 hospitals. Follow-up identified cancer recurrence and death. A baseline model for cancer recurrence at 3 years was developed from pre-specified clinicopathological variables (age, sex, tumour-node stage, tumour size, location, extramural venous invasion, and treatment). Then, CT perfusion (blood flow, blood volume, transit time and permeability), genetic (RAS, RAF, and DNA mismatch repair), and immunohistochemical markers of angiogenesis and hypoxia (CD105, vascular endothelial growth factor, glucose transporter protein, and hypoxia-inducible factor) were added to assess whether prediction improved over tumour-node staging alone as the main outcome measure. RESULTS: Three hundred twenty-six of 448 participants formed the final cohort (226 male; mean 66 ± 10 years. 227 (70%) had ≥ T3 stage cancers; 151 (46%) were node-positive; 81 (25%) developed subsequent recurrence. The sensitivity and specificity of staging alone for recurrence were 0.56 [95% CI: 0.44, 0.67] and 0.58 [0.51, 0.64], respectively. The baseline clinicopathologic model improved specificity (0.74 [0.68, 0.79], with equivalent sensitivity of 0.57 [0.45, 0.68] for high vs medium/low-risk participants. The addition of prespecified CT perfusion, genetic, and immunohistochemical markers did not improve prediction over and above the clinicopathologic model (sensitivity, 0.58-0.68; specificity, 0.75-0.76). CONCLUSION: A multivariable clinicopathological model outperformed staging in identifying patients at high risk of recurrence. Promising CT, genetic, and immunohistochemical markers investigated did not further improve prognostication in rigorous prospective evaluation. CLINICAL RELEVANCE STATEMENT: A prognostic model based on clinicopathological variables including age, sex, tumour-node stage, size, location, and extramural venous invasion better identifies colorectal cancer patients at high risk of recurrence for neoadjuvant/adjuvant therapy than stage alone. KEY POINTS: Identification of colorectal cancer patients at high risk of recurrence is an unmet need for treatment personalisation. This model for recurrence, incorporating many patient variables, had higher specificity than staging alone. Continued optimisation of risk stratification schema will help individualise treatment plans and follow-up schedules.

Can 99mTc-DTPA aerosol scanning predict radiation pneumonitis?

PURPOSE: To investigate whether changes in diethylenetriamine pentaacetic acid (DTPA) aerosol clearance lung scans predict the development of radiation pneumonitis. METHODS AND MATERIALS: Thirty-three patients with advanced non-small-cell lung cancer were treated with palliative radiation therapy to thorax. All patients were subjected to pretreatment and post-treatment DTPA aerosol clearance lung scans. The clearance t1/2 values were compared using the paired t test. Changes in percentage aerosol deposition were also compared. The patients were serially assessed clinically and radiologically for development of radiation pneumonitis. RESULTS: For the whole group, the mean DTPA clearance t1/2 for the diseased lung fell from 36.33 to 28.85 min (p = 0.17). Twelve patients developed radiation pneumonitis, 8 Grade 1, 2 Grade 2, 1 Grade 3, and 1 Grade 4. In patients who developed radiation pneumonitis, the clearance t1/2 for the diseased lung decreased from 37.50 min to 29.00 min after treatment (p = 0.50). Other subgroups analyzed, including smokers, nonsmokers, those with and without endobronchial disease, as well as those free from radiation pneumonitis, also showed no significant change in the clearance of the aerosol. The difference between the percentage aerosol deposition of the diseased lung (37.92%) and that of the opposite lung (62.08%) for the entire sample was significantly different both before and after treatment (p < 0.01). Delivery of radiation did not significantly change the aerosol deposition in either lung. CONCLUSIONS: We conclude that, in patients with advanced non-small-cell lung cancer, significant change in the pulmonary clearance of 99mTc-DTPA aerosol could not be demonstrated after radiation therapy. In such patients, clearance of the aerosol does not predict the development of radiation pneumonitis.

Dose-dense and dose-intense chemotherapy for small cell ovarian cancer: 2 cases and review of literature.

Small cell carcinomas of the ovary (SCCO) are rare and aggressive malignant neoplasms carrying a poor prognosis. Although multi-modality treatment including chemotherapy leads to a high initial response rate, the majority of these patients relapse quickly and die within 2 years of diagnosis. Because these tumours are rare, there is no consensus to support any particular approach to management. We present 2 cases and review the relevant literature to make a number of recommendations. The treatment of these unusual cases should to be individually discussed in a multi-disciplinary team and multi-modality treatment including surgery, chemotherapy and radiotherapy should be considered for patients with limited disease. Conservative, fertility-preserving surgery may be considered in younger women with early-stage disease. Induction chemotherapy with weekly dose-dense and dose-intense carboplatin and taxane is useful. Prophylactic cranial irradiation (PCI) may be considered in patients in remission after primary treatment with chemotherapy or surgery.

Positron emission tomography with computed tomography (PET-CT) to evaluate the response of bone metastases to non-surgical treatment.

A case of solitary bone metastasis from breast cancer, where MRI assessment of treatment response was inaccurate and whole-body fluorodeoxyglucose ((18)FDG) positron emission tomography with computed tomography (PET-CT) proved more reliable and objective, is presented.