Francesca Di Salvo

Age and case mix-standardised survival for all cancer patients in Europe 1999–2007: Results of EUROCARE-5, a population-based study

BACKGROUND Overall survival after cancer is frequently used when assessing a health care services performance as a whole. It is mainly used by the public, politicians and the media, and is often dismissed by clinicians because of the heterogeneous mix of different cancers, risk factors and treatment modalities. Here we give survival details for all cancers combined in Europe, correlating it with economic variables to suggest reasons for differences. METHODS We computed age and cancer site case-mix standardised relative survival for all cancers combined (ACRS) for 29 countries participating in the EUROCARE-5 project with data on more than 7.5million cancer cases from 87 population-based cancer registries, using complete and period approach. RESULTS Denmark, United Kingdom (UK) and Eastern European countries had lower survival than neighbouring countries. Five-year ACRS has been increasing throughout Europe, and substantial increases, between 1999-2001 and 2005-2007, have been achieved in countries where survival was lower in the past. Five-year ACRS for men and women are positively correlated with macro-economic variables like the Gross Domestic Product (GDP) and Total National Expenditure on Health (TNEH) (R2 about 70%). Countries with recent larger increases in GDP and TNEH had greater increases in cancer survival. CONCLUSIONS ACRS serves to compare all cancer survival in Europe taking account of the geographical variability in case-mixes. The EUROCARE-5 data on ACRS confirm previous EUROCARE findings. Survival appears to correlate with macro-economic determinants, particularly with investments in the health care system.

A method for differentiating cancer prevalence according to health status, exemplified using a population-based sample of Italian colorectal cancer cases

Abstract Cancer prevalence is the proportion of a population diagnosed with cancer. We present a method for differentiating prevalence into the proportions expected to survive without relapse, die of cancer within a year, and die of cancer within 10 years or survive with relapse at the end of the 10th year. Material and methods. The method was applied to samples of colorectal cancer cases, randomly extracted from four Italian cancer registries (CRs). The CRs collected data on treatments, local relapses, distant relapses, and causes of death: 1) over the entire follow-up to 31 December 2007 for 601 cases diagnosed in 2002 (cohort approach); 2) over a single year (2007) for five cohorts of cases defined by year of diagnosis (from 1997 to 2001), alive at 1 January 2007 (total 298 cases). The cohorts were combined into a fictitious cohort with 10 years survival experience. For each year j after diagnosis the health status of cases alive at the beginning of j was estimated at the end of the 10th year. From these estimates the 10-year colorectal cancer prevalence was differentiated. Results. We estimated: 74.7% alive without relapse or not undergoing treatment at the end of 10 years; 8.1% had died of colorectal cancer within a year; 11.4% had died of colorectal cancer 1–10 years after diagnosis or had relapsed or were undergoing treatment at the end of the 10th year; and 5.8% had died of other causes. Conclusions. We have introduced a new method for estimating the healthcare and rehabilitation demands of cancer survivors based on CR data plus treatment and relapse data specifically collected for samples of cases archived by CRs.

Cancer research performance in the European Union: a study of published output from 2000 to 2008.

AIMS AND BACKGROUND Although several studies have assessed cancer research performance in individual European countries, comparisons of European Union (EU27) performance with countries of similar population size are not available. METHODS We compared cancer research performance in 2000-2008 between EU27 and 11 countries with over 100 million inhabitants. Performance should not have been affected by the 2007-2009 recession. We examined 143 journals considered oncology journals by Journal Citation Reports, accessing them via Scopus. Publications were attributed to countries using a published counting procedure. RESULTS For number of publications, the USA held a clear lead in 2006-2008 (yearly averages: 10,293 USA vs 9,962 EU27), whereas the EU27 held the lead previously. EU27 was also second to the USA for total impact factor. China markedly improved its cancer publications record over the period. Compared to the USA, EU27 and Japan, the other countries (all developing) had a poor publications record. CONCLUSIONS Comparative cancer research spending data are not available. However from 2002 to 2007, gross domestic expenditure on research and development (UNESCO data) increased by 34% in North America, 161% in China and only 28% in EU27. Thus the European Union is lagging behind North America and may well be eclipsed by China in research and development spending in the near future. We suggest that these new findings should be considered by policymakers in Europe and other countries when developing policies for cancer control.

Trastuzumab and Hypofractionated Whole Breast Radiotherapy: A Victorious Combination?

Micro‐Abstract Radiotherapy (RT) and trastuzumab are usually administered concurrently in patients with human epidermal growth factor receptor‐2‐positive breast cancer. Adjuvant hypofractionated RT, delivered in 15 or 16 fractions, has been accepted as a valid alternative to standard fractionation. We examined the feasibility of associating hypofractionated RT with trastuzumab, finding a safe profile in terms of acute skin and cardiac toxicity. Introduction: The purpose of this study was to examine the impact of trastuzumab on acute skin and cardiac toxicity in patients with breast cancer treated with chemotherapy with or without trastuzumab and adjuvant whole breast hypofractionated radiotherapy (hypo‐RT). Materials and Methods: The study was conducted on 727 patients treated from April 2009 to October 2016. Patients received 42.4 Gy in 16 daily fractions (2.65 Gy per fraction). A boost was only administered in cases with grade (G) 3 primary tumor and close or positive margins. Acute and late toxicity was assessed prospectively during and after hypo‐RT, based on the Radiation Therapy Oncology Group scale. Multivariable logistic regression models were used to examine the onset of acute skin toxicity (≥ G2) in the whole study population, and the impact of trastuzumab on the onset of acute skin (≥ G2) or cardiac toxicity in the subgroup of 176 patients given chemotherapy. Results: A total of 176 patients received chemotherapy with anthracycline and taxane, and 51 (29%) of them were also treated with trastuzumab. Acute G1, G2, and G3 skin toxicity occurred, respectively, in 56.8%, 27.3%, and 1.1% of the patients given chemotherapy alone, and in 64.7%, 19.6%, and 0% of those given trastuzumab as well. Among the patients given chemotherapy, left ventricular ejection fraction (LVEF) toxicity developed with a severity of G1 (LVEF < 60%‐50%) in 12 (6.8%) patients, G2 (LVEF < 50%‐40%) in 2 (1.1%) patients, and G3 (LVEF < 40%) in 1 (0.6%) patient. Among the patients also given trastuzumab, 7 (13.7%) patients had G1 LVEF toxicity, and 1 (2%) patient had G2 LVEF toxicity. We found that patients given trastuzumab were at higher risk of cardiac toxicity ≥ G1 (odds ratio, 4.3; P = .01), and at lower risk of acute skin toxicity ≥ G2 (odds ratio, 0.4; P = .03) than patients given chemotherapy alone. Conclusions: This analysis showed that trastuzumab with adjuvant hypo‐RT for patients with breast cancer was generally well‐tolerated in routine clinical practice. A longer follow‐up will be necessary to assess late cardiac toxicity.

Hypofractionated Whole-Breast Irradiation With or Without Boost in Elderly Patients: Clinical Evaluation of an Italian Experience

Purpose To examine local control, disease‐free survival (DFS), and toxicity in elderly (≥ 65 years) breast cancer patients treated with hypofractionated radiotherapy (hypo‐RT) with or without a boost to the tumor bed. Patients and Methods The study was conducted on 752 patients treated from April 2009 to February 2017. Patients received 42.4 Gy in 16 daily fractions (2.65 Gy per fraction). A boost was only administered in cases of grade 3 primary tumor and close or positive margins. Acute and late toxicity was prospectively assessed during and after hypo‐RT, based on the Radiation Therapy Oncology Group scale. DFS and local recurrence–free survival were estimated by the Kaplan‐Meier method for cumulative probability. Log‐rank tests were used to identify differences by subtype. Cox proportional hazard models were used to investigate the impact of various factors on the risk of disease progression. Results Among the 752 patients treated, 41 (5.5%) experienced disease progression, including 7 (17.1%) exclusively local recurrences; 1 (2.4%) local and nodal recurrence; 1 (2.4%) local and nodal recurrence plus metastasis; 7 (17.1%) nodal recurrences plus metastases; and 25 (61%) exclusively distant metastases. The 5‐year DFS, local recurrence–free survival, breast cancer–specific survival, and overall survival rates were 91.8% (95% confidence interval [CI], 88.6‐94.2), 98.0% (95% CI, 96.1‐99.1), 98.2% (95% CI, 96.5‐99.1), and 87.5% (95% CI, 83.8‐90.5), respectively. On univariate analysis, the administration of a boost, disease grade (grades 1 and 2 vs. 3), and molecular subtype (triple negative or human epidermal growth factor receptor 2 [HER2] positive, or luminal B vs. luminal A) significantly affected disease progression (P < .01). These findings were confirmed by multivariate analysis. Conclusion Hypo‐RT is effective and well tolerated in the elderly population, and the routine use of a boost for patients over 65 years is not justified. Further studies on the boost issue are strongly advocated. Micro‐Abstract To examine local control, disease‐free survival, and toxicity in breast cancer patients aged ≥ 65 years treated with hypofractionated radiotherapy, we assessed 752 patients. Univariate and multivariate analysis revealed that the administration of a boost, disease grade, and molecular subtype significantly affected disease progression. Hypofractionated radiotherapy is effective and well tolerated in the elderly population.

Cancer rehabilitation services: An Italian population-based cohort study

Aims and Background In Italy more than 55% of cancer patients live for more than 5 years after diagnosis, sometimes with several cancer-related sequelae. For this reason rehabilitation must offer not only physical interventions but also psychological, clinical, social and nutritional support. The CAREMORE pilot study was designed to assess whether cancer registries could serve to collect information on rehabilitation services, to describe and quantify the services provided by the National Health Service, and to examine the allocation of rehabilitation services to cancer patients. Methods and Study Design This was a pilot population-based cohort study. A sample of 1200 patients was identified from the databases of the Varese, Genoa, Reggio Emilia, Sassari and Ragusa cancer registries, all diagnosed in 2002 and followed for 5 years. For 4 cancer sites a list of rehabilitation items to be collected was drafted by a joint community of researchers and voluntary associations, with variables regarding rehabilitation data and follow-up. Data were analyzed by groups of patients, vital status, sex, and age. Results This pilot study suggested it is useful to collect information on several rehabilitation services: disability benefits, home care, aids and other support; it was not possible to collect reliable information on nutritional and psychological rehabilitation. In all, 36% of the sample applied for disability benefits, but with important differences between cancer sites. Eleven percent of the sample obtained home care, with no substantial differences between cancer sites, and 16% received at least one aid, with percentages varying from 27% for rectal cancer to 8% for lymphoma patients. Conclusions The pilot study indicated that cancer registries could collect information on rehabilitation services. In the future it would be interesting to expand the roles of these registries to factors that influence quality of life, taking into account the possibility of collecting more information by actually interviewing patients.

Socioeconomic deprivation worsens the outcomes of Italian women with hormone receptor-positive breast cancer and decreases the possibility of receiving standard care

Background Socioeconomic factors influence access to cancer care and survival. This study investigated the role of socioeconomic status on the risk of breast cancer recurrence and on the delivery of appropriate cancer care (sentinel lymph node biopsy and breast-conserving surgery plus radiotherapy), by patients’ age and hormone receptor status. Methods 3,462 breast cancer cases diagnosed in 2003-2005 were selected from 7 Italian cancer registries and assigned to a socioeconomic tertile on the basis of the deprivation index of their census tract. Multivariable models were applied to assess the delivery of sentinel lymph node biopsy and of breast-conserving surgery plus radiotherapy within socioeconomic tertiles. Results In the 1,893 women younger than 65 years, the 5-year risk of recurrence was higher in the most deprived group than in the least deprived, but this difference was not significant (16.4% vs. 12.9%, log-rank p=0.08); no difference was seen in women ≥65 years. Among the 2,024 women with hormone receptor-positive cancer, the 5-year risk was significantly higher in the most deprived group than in the least deprived one (13.0% vs. 8.9%, p=0.04); no difference was seen in cases of hormone receptor-negative cancer. The most deprived women were less likely than the least deprived women to receive sentinel lymph node biopsy (adjusted odds ratio (ORa), 0.69; 95% CI, 0.56-0.86) and to undergo breast-conserving surgery plus radiotherapy (ORa=0.66; 95% CI, 0.51-0.86). Conclusions: Socioeconomic inequalities affect the risk of recurrence, among patients with hormone receptor-positive cancer, and the opportunity to receive standard care.

Neoadjuvant Chemotherapy Exerts Selection Pressure Towards Luminal Phenotype Breast Cancer

Background: Breast cancer (BC) phenotype after neoadjuvant chemotherapy (NAC) has not been extensively described and few data exist on whether expression of the primary tumor hormone receptors, HER2 and Ki-67 changes as a result of chemotherapy. Materials and Methods: We analyzed specimens from all BC patients treated with anthracycline/taxane-based NAC at our Institution between January 2010 and March 2015 (n = 325). The expression of estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki-67 was determined in pre- and post-NAC specimens. McNemars test was used to compare paired proportions. Results: Among patients with residual disease after NAC, basal phenotype was luminal A, luminal B, HER2 positive and triple negative in 44, 111, 74 and 27 cases, respectively. PR-positive tumors decreased from 68.0% in the initial biopsy sample to 61.7% in the surgical specimen (p = 0.024). A Ki-67 of < 20% increased from 23.6% to 45% (p < 0.001). ER expression changed from positive to negative in 5% and from negative to positive in 16.7% of cases. Overall, 30% of cases underwent subtype changes, 79% of them towards luminal differentiation. Conclusions: The switch towards luminal phenotype suggests some kind of endocrine effect of NAC. Our findings raise renewed interest in combinatorial cytotoxic chemotherapy with concomitant or rather sequential endocrine therapy, either alone or with targeted agents.