AIM:Induction chemotherapy (IC) added to chemoradiation (CRT) in locally advanced cervical cancer (LACC) improves survival at the expense of adverse events (AEs), 99 % with IC/CRT vs 95 % CRT alone, 59 % vs 48 % G3/4 AEs. We investigated the impact of this on quality of life (QoL). METHODS:500 women with FIGO 2008 stage IB1 node positive, IB2, II, IIIB and IVA cervical carcinoma were randomised to CRT alone or IC (6 weeks carboplatin AUC2 paclitaxel 80mg/m2) followed by CRT. QoL questionnaires (EORTC QLQ-C30 v3, QLQ-CX24) were completed at baseline, D1 week 4 IC, D1 CRT, D1 week 3 CRT, 4 weeks post CRT and all follow up visits. Mixed modelling for repeated measures was used to compare the groups during trial treatment to 2 years follow up (adjusting for baseline). RESULTS:QoL (global health status, physical and social functioning) slightly worsened during IC and symptom experience slightly improved. Emotional functioning improved during IC. Peripheral neuropathy was slightly worse with IC/CRT. Fatigue and nausea/vomiting worsened from baseline to week 4 IC whilst pain and diarrhoea improved, consistent with reported AEs. Over the whole period, mean differences for these symptoms between the treatment groups was small and not clinically significant and resolved by 12-18 months. In all cases, mean score differences during trial treatment until 2 years post CRT showed only small differences (<5 units) not meeting the threshold for clinical relevance. CONCLUSION:IC added to CRT does not adversely impact QoL compared to CRT, either during IC, during CRT or later.

We have performed a quality of life (QOL) substudy investigating change in patient reported outcomes (PROs) up to 5 years in the Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer (CHHiP) trial. A total of 3213 men with localized prostate cancer were randomly assigned (1:1:1) to receive 74Gy in 37 fractions, 60Gy in 20 fractions or 57Gy in 19 fractions. A total of 2100 patients were recruited into the QOL substudy. UCLA Prostate Cancer Index (UCLA-PCI), Short Form (SF)-36 and Functional Assessment of Cancer Therapy-Prostate (FACT-P), or Expanded Prostate Cancer Index Composite (EPIC) and SF-12 quality-of-life questionnaires were completed at baseline and multiple time points up to 5 years post-radiotherapy. Analysis was on an intention-to-treat basis. Odds of change in symptoms (post-radiotherapy score at each time point minus baseline score) were compared between treatment arms using ordinal logistic regression; analysis of covariance was used to assess change over time for the domain scores, adjusting for baseline/pre-radiotherapy score. A total of 1138 (73%) of the expected 1557 forms were available at 5 years: 352 for 74Gy, 386 for 60Gy and 400 for 57Gy. There was no significant difference in the prevalence or cumulative incidence of patients with overall “moderate or big” bowel, urinary or sexual bother at 5-years between the three arms. There was no significant difference in the odds of "increase in score" from baseline to 5-years for overall bowel or urinary bother between the three arms (Table), and no evidence of an increase in bowel or urinary symptoms from 2 to 5-years. There was some evidence of a larger deterioration in overall sexual function in the 74 Gy arm compared to both hypofractionated arms, which was most marked for sexual bother (Table). Sexual function appeared to deteriorate across all arms between 2 and 5-years. There were no significant differences in general QOL domain scores between arms at 2 and 5 years. Change in bowel or urinary symptoms up to 5 years was similar between the treatment schedules in the CHHiP trial, but there was evidence of less decline in sexual function for the hypofractionated arms compared with the control arm. This supports the use of moderately hypofractionated radiotherapy for localized prostate cancer.Abstract 2; TableOrdinal logistic regression to show odds of "increase in score" from baseline to 5 years for each paired comparison of treatment groupsItemComparisonOdds ratio (99% CI)P-ValueOverall bowel bother60 Gy vs 74 Gy 57 Gy vs 74 Gy 57 Gy vs 60 Gy0.78 (0.52, 1.18) 0.75 (0.50, 1.12) 0.96 (0.64, 1.44)0.12 0.06 0.80Overall urinary bother60 Gy vs 74 Gy 57 Gy vs 74 Gy 57 Gy vs 60 Gy1.00 (0.67, 1.50) 1.08 (0.72, 1.61) 1.09 (0.73, 1.62)>0.99 0.62 0.58Overall sexual bother60 Gy vs 74 Gy 57 Gy vs 74 Gy 57 Gy vs 60 Gy0.55 (0.30, 0.99) 0.52 (0.29, 0.94) 0.95 (0.53, 1.70)0.009 0.004 0.82 Open table in a new tab

Aim: Patients with extremely high PSA (>100) are at significant risk of harbouring overt or occult metastatic disease. In the past, many clinical trials excluded patients with PSA >50 and many clinicians did not offer radical radiotherapy to patients with a very high PSA, even if there was no radiologically overt metastatic disease. No prospective trial has reported the outcomes specifically for this ‘extremely high risk’ group of patients with a presenting PSA >100.

To report toxicities, cosmetic outcomes and local control in a series of patients treated on a pilot study of partial breast irradiation (PBI), using CT-planned high-dose-rate (HDR) multi-catheter interstitial brachytherapy. Between May 2003 and December 2005, 30 subjects with low-risk breast cancer were treated with adjuvant PBI using multi-catheter interstitial HDR brachytherapy. All subjects fulfilled the following criteria: age >50 years; invasive ductal histology; T <3cm, pN0; ER positive; LVI negative; and surgical margin >0.2cm. Pre-implant CT was performed 4-8 weeks following breast-conserving surgery. The PTV was the excision cavity + 1.5cm, excluding chest wall and 0.5 cm from skin. An ideal virtual implant was created based on the Paris System. Post-implant CT planning was performed, delivering 32.4Gy in 9 BID fractions over 5 days, using an Iridium-192 HDR after-loading system. Acute toxicity (NCI criteria), late morbidity (RTOG) and overall cosmesis (EORTC) were prospectively evaluated and recurrence rates have been updated. Mean tumor size was 1.2cm (0.4 - 2.4cm). Acute toxicities at 6 weeks and 3 months were all grade 1: fatigue (7%, 0%); pain due to radiation (4%, 7%) and radiation dermatitis (7%, 0%). Telangiectasia was observed in two subjects (7%), maximum dimension 3.5 and 2.0cm, 25 and 37 months after treatment. Fat necrosis occurred in 3 subjects (10%), 13, 16 and 68 months after treatment, one undergoing mastectomy. Cosmesis was good-excellent in 82% of patients at baseline; while 89% had stable or improved cosmesis at three years compared to baseline. At a median follow-up of 80 months (range 60-90 months), patient and disease status were as follows: 32 months after diagnosis, one subject developed an ipsilateral breast node-positive tumor in a different quadrant which was pathologically distinct from the original tumor; salvaged with mastectomy, axillary dissection and post-operative RT. Another subject developed nodal-only recurrence at 42 months, salvaged with axillary dissection and post-operative RT. A third developed lung and bone metastases 49 months after diagnosis and died 8 months later. None of the subjects experienced recurrence in the same quadrant as the index tumor. In this cohort of women with favorable-risk breast cancer, PBI with CT-planned interstitial HDR brachytherapy provided excellent local control, good-excellent cosmesis and acceptable acute and late toxicities.

The evidence to support any specific cervix high dose rate (HDR) brachytherapy schedule has never been very strong, leading to a wide variety of fractionation schedules. We present survival and toxicity data in a sample of patients treated with 2 fractions of HDR brachytherapy, the schedule routinely used in our institution since 2001. We included all consecutive patients (since August 2001) treated radically in our department with external beam radiotherapy (EBRT) to the pelvis and concomitant weekly cisplatin chemotherapy followed by HDR Brachytherapy. Data prior to January 2005 was collected retrospectively, and prospectively beginning at that date. Only patients with at least 18 months of follow-up were included. 3 and 5 year Kaplan-Meier overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), including local recurrence-free survival (LRFS) and distant recurrence-free survival (DRFS) were analyzed. Long-term genitourinary (GU) and gastrointestinal (GI) toxicity was measured. We performed a univariate analysis, by application of log–rank statistic, to identify potential prognostic factors. Multivariate analyses were performed using Cox proportional hazards modeling in those factors that showed significance on univariate analysis. 82 patients (FIGO Stage IB-IVA) were identified, EBRT median dose was 46 Gy (46–50 Gy). Chemotherapy was prescribed in 68 (14 were not considered to be fit). Prescribed dose, for each HDR Brachytherapy fraction, to point A, was 8.5 Gy. A parametrial EBRT boost was used in 2 cases, with a median dose of 8 Gy. In 3 cases with enlarged para-aortic lymph nodes, they were treated with EBRT as well, with a median dose of 46 Gy (45–60 Gy). Median rectal and bladder doses were 5.54 Gy (3.30–7.73) and 6.14 Gy (2.60–7.57) per fraction. Median treatment time was 44 days (30–72 days). Median follow-up was 35.9 months. 3 and 5-year overall OS was are 70.3% and 54.4%; the 3 and 5-year DSS was 79.8% and 70.9%; the 3 and 5-year LRFS was 87.4% and 85.2% and the 3 and 5-year DRFS was 85.4% and 78.0% (all actuarial values). RTOG Grade 3–4 GI and GU toxicity was identified in 5 patients (6.2%) and 9 patients (11.1%), respectively. Radical treatment for cervix cancer with chemo-radiotherapy and 2 fractions of HDR brachytherapy appears to be an effective approach. The reported toxicity was slightly higher than reported in some other series. Larger HDR fractions could account for this extra toxicity. 3D conformal Brachytherapy planning has been proven to reduce toxicity and it should be explored in this setting. It could enable a safe minimization of overall treatment time and it could lead to a more efficient use of finite oncological resources.

PURPOSE:To define the individual factors and combinations of factors associated with increased risk of locoregional recurrence (LRR) that may justify postmastectomy radiotherapy (PMRT) in patients with T1-T2 breast cancer and one to three positive nodes. METHODS AND MATERIALS:The study cohort comprised 821 women referred to the British Columbia Cancer Agency between 1989 and 1997 with pathologic T1-T2 breast cancer and one to three positive nodes treated with mastectomy without adjuvant RT. The 10-year Kaplan-Meier estimates of isolated LRR and LRR with or without simultaneous distant recurrence (LRR +/- SDR) were analyzed according to age, histologic findings, tumor location, size, and grade, lymphovascular invasion status, estrogen receptor (ER) status, margin status, number of positive nodes, number of nodes removed, percentage of positive nodes, and systemic therapy use. Multivariate analyses were performed using Cox proportional hazards modeling. A risk classification model was developed using combinations of the statistically significant factors identified on multivariate analysis. RESULTS:The median follow-up was 7.7 years. Systemic therapy was used in 94% of patients. Overall, the 10-year Kaplan-Meier isolated LRR and LRR +/- SDR rate was 12.7% and 15.9%, respectively. Without PMRT, a 10-year LRR risk of >20% was identified in women with one to three positive nodes plus at least one of the following factors: age <45 years, Stage T2, histologic Grade 3, ER-negative disease, medial location, more than one positive node, or >25% of nodes positive (all p < 0.05 on univariate analysis). On multivariate analysis, age <45 years, >25% of nodes positive, medial tumor location, and ER-negative status were statistically significant predictors of isolated LRR and LRR +/- SDR. In the classification model, the first split was according to age (<45 years vs. >/=45 years), with 29.3% vs. 13.7% developing LRR +/- SDR (p < 0.0001). Of 123 women <45 years, the presence of >25% of nodes positive was associated with a risk of LRR +/- SDR of 58.0% compared with 23.8% for those with =25% of nodes positive (p = 0.01). Of 698 women >45 years, the presence of >25% of nodes positive also conferred a greater LRR +/- SDR risk (26.7%) compared with women with =25% of nodes positive (10.8%; p < 0.0001). In women >45 years with =25% of nodes positive, tumor location and ER status were factors that could be used to further distinguish low-risk from higher risk subsets. CONCLUSION:Clinical and pathologic factors can identify women with T1-T2 breast cancer and one to three positive nodes at high LRR risk after mastectomy. Age <45 years, >25% of nodes positive, a medial tumor location, and ER-negative status were statistically significant independent factors associated with greater LRR, meriting consideration and discussion of PMRT. Combinations of these factors further augmented the LRR risk, warranting recommendation of PMRT to optimize locoregional control and potentially improve survival. The absence of high-risk factors identifies women who may reasonably be spared the morbidity of PMRT.

PURPOSE:To determine if mastectomy (Mx) use, chemotherapy (CT) intensity, or treatment sequence of CT, radiation therapy (RT), and Mx have improved outcome for inflammatory breast cancer (IBC).PATIENTS AND METHODS:A retrospective analysis of 485 patients with IBC diagnosed in British Columbia between 1980 and 2000 analyzed locoregional relapse-free survival (LRFS) and breast cancer-specific survival (BCSS) by treatment intent and treatment received. Curative intent was defined as delivery of more than four cycles of anthracycline-based CT plus locoregional RT in patients without distant metastases.RESULTS:Median follow-up among survivors was 6.5 years. Median BCSS was 1.0 and 3.2 years for patients with distant metastases at diagnosis or those who were curatively treated, respectively. Among patients treated curatively (n = 308), there were no significant differences in LRFS or BCSS with timing of Mx before or after CT/RT, time between diagnosis and RT, or the sequence of RT and CT. Patients receiving more intensive CT had improved 10-year BCSS compared with standard CT (43.7% v 26.3%; P = .04). Ten-year LRFS for patients having Mx after CT, Mx before CT, and without Mx was 62.8%, 58.6%, and 34.4%, respectively (P = .0001); the corresponding 10-year BCSS was 36.9%, 19.9%, and 22.5%, respectively (P = .005). On multivariate analysis, Mx was associated with improved LRFS (P = .04). Independent prognostic factors for BCSS were menopausal status (P = .02), estrogen receptor status (P = .02), and CT type (P = .05).CONCLUSION:This retrospective analysis suggested that mastectomy, in conjunction with CT and RT, seemed to enhance locoregional control, whereas modern CT regimens seemed to improve BCSS.