Role of neoadjuvant therapy in the management of pancreatic cancer: is the era of biomarker-directed therapy here?

Pancreatic cancer is the 4th leading cause of cancer-related death. Complete surgical resection (CR0) is considered the only curative treatment. Most patients present with unresectable or borderline resectable disease. Many small phase i/ii trials have tried to address the role of neoadjuvant treatment using chemotherapy with or without chemoradiation in the management of locally advanced disease. However, many of them looked at the rate of CR0 resection and the feasibility of such treatment. A trend for improved overall survival has been observed in the group of patients with borderline resectable disease who completed neoadjuvant treatment. A large proportion of patients progress while on treatment, sparing them from unnecessary surgery.We searched the PubMed database (using the key words “pancreatic cancer,” or “pancreatic neoplasm,” or “pancreatic adenocarcinoma,” and “neoadjuvant treatment,” or “neoadjuvant chemotherapy,” or “neoadjuvant radiation therapy,” or “neoadjuvant chemo-radiation,” or “adjuvant therapy” [all fields] and “clinical trial” or “study”) and abstracts presented at the American Society of Clinical Oncology meetings on gastrointestinal cancers. Here, we review the most recent papers that present results on neoadjuvant therapy in pancreatic cancer. All but one report used overall survival as an endpoint. Unfortunately, there are no valid biomarkers predicting tumour progression or recurrence, and response to treatment than can help to guide therapeutic choices.Our recommendation is to consider neoadjuvant treatment in cases of borderline resectable disease. In patients with primary resectable tumours, surgery followed by adjuvant treatment and enrollment on adjuvant treatment studies would be appropriate.     

Recommendations for Palliative and Hospice Care in NCCN Guidelines for Treatment of Cancer

BackgroundIntegration of specialist palliative care into routine oncologic care improves patients’ quality of life and survival. National Comprehensive Cancer Network (NCCN) cancer treatment guidelines are instrumental in standardizing cancer care, yet it is unclear how palliative and hospice care are integrated in these guidelines. In this study, we examined the frequency of occurrence of “palliative care” and “hospice care” in NCCN guidelines and compared between solid tumor and hematologic malignancy guidelines.Materials and MethodsWe reviewed all 53 updated NCCN Guidelines for Treatment of Cancer. We documented the frequency of occurrence of “palliative care” and “hospice care,” the definitions for these terms if available, and the recommended timing for these services.ResultsWe identified a total of 37 solid tumor and 16 hematologic malignancy guidelines. Palliative care was mentioned in 30 (57%) guidelines (24 solid tumor, 6 hematologic). Palliative care was mentioned more frequently in solid tumor than hematologic guidelines (median, 2 vs. 0; p = .04). Among the guidelines that included palliative care in the treatment recommendation, 25 (83%) only referred to NCCN palliative care guideline. Specialist palliative care referral was specifically mentioned in 5 of 30 (17%) guidelines. Only 14 of 24 (58%) solid tumor guidelines and 2 of 6 (33%) hematologic guidelines recommended palliative care in the front line setting for advanced malignancy. Few guidelines (n = 3/53, 6%) mentioned hospice care.Conclusion“Palliative care” was absent in almost half of NCCN cancer treatment guidelines and was rarely discussed in guidelines for hematologic malignancies. Our findings underscored opportunities to standardize timely palliative care access across NCCN guidelines.Implications for PracticeIntegration of specialist palliative care into routine oncologic care is associated with improved patient outcomes. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology have an important role to standardize palliative care involvement for cancer patients. It is unclear how often palliative care referral is recommended in these guidelines. In this study involving 53 NCCN Guidelines for Treatment of Cancer, the researchers found that palliative care was not mentioned in over 40% of NCCN guidelines and was rarely discussed in guidelines for hematologic malignancies. These findings underscored opportunities to standardize timely palliative care access across NCCN guidelines.     

Surveillance for asymptomatic recurrence in resected stage III colon cancer: does it result in a more favorable outcome?

Background

Evidence from dated and moderate quality trials supports a modest survival benefit for intensive surveillance in resected colon cancer (CC). This study evaluates surveillance in a modern population-based cohort of stage III CC patients (pts).

Methods

Records of pts who initiated oxaliplatin-based adjuvant chemotherapy (AC) for stage III CC between 2006-2011 at the British Columbia Cancer Agency (BCCA) were reviewed. Kaplan-Meier and log rank test were generated to investigate whether diagnosis of recurrence based on symptoms was associated with worse overall survival (OS). OS1 and OS2 were measured from date of recurrence or date of initial surgery, respectively.

Results

Of 635 pts who received AC for stage III CC, 175 pts (27.5%) recurred and 118 (18.6%) died at a median follow-up of 67.7 months. Recurrences were detected by surveillance in 149 pts (41% by CEA elevation and 44% by abnormal imaging), and symptoms in 26 pts (15%). Patients with surveillance-detected recurrences had a shorter median relapse-free survival (RFS) (18.5 vs. 25.3 months, HR 1.82, P<0.001), and longer median OS1 (28.5 vs. 6.5 months, HR 0.37, P<0.001). However, median OS2 was not significantly different (50.9 vs. 39.1 months, HR 0.66, P=0.091). Pts with surveillance-detected recurrence received more potentially curative metastasectomy (39% vs. 7%, P=0.002) and chemotherapy (70% vs. 50%, P=0.03).

Conclusions

In this modern population-based cohort study, the OS impact of detecting asymptomatic recurrences in stage III CC is unclear. However, pts with asymptomatic recurrences were more likely to receive potentially curative metastasectomy and chemotherapy.     

Surveillance of the current situation regarding influenza vaccination according to medical oncologists in Japan

This study aimed to clarify the attitude of oncologists toward influenza vaccination and the current situation and issues regarding influenza vaccination for patients on chemotherapy in Japan. A web‐based survey of medical oncologists certified by the Japanese Society of Medical Oncology was conducted between November 1 and December 31, 2019. Of the 1369 medical oncologists who were invited to participate, 415 (30.3%) responded to our survey. The questionnaire comprised 4 sections: “oncologist characteristics,” “oncologist attitude toward influenza vaccines and the current status of influenza vaccination for cancer patients undergoing chemotherapy,” “incidence of influenza infection and associated treatment complications,” and “treatment policy for influenza infection.” In total, 153 (36.9%) physicians replied that they did not actively encourage influenza vaccination for patients undergoing chemotherapy. The primary reasons given were lack of evidence (48/153, 31.4%) and uncertainty of appropriate timing (46/153, 30.1%). There was diverse variation in the timing of vaccination and in the levels of encouragement based on the cancer location and medication type. Two hundred eighty‐three (68.2%) oncologists reported that their cancer patients had experienced influenza infection while undergoing chemotherapy, and 169 (40.7%) responded that their patients had experienced an administration delay or discontinuation of medication because of influenza infection. Our surveillance revealed some oncologists considered evidence regarding the administration of influenza vaccine to cancer patients undergoing chemotherapy (particularly the optimal timing and level of recommendation by cancer location and medication) to be lacking. It also exposed the adverse impact of influenza infection in cancer patients.     

Use of screening tests,diagnosis wait times,and wait-related satisfaction in breast and prostate cancer

Background

Understanding factors relating to the perception of wait time by patients is key to improving the patient experience.

Methods

We surveyed 122 breast and 90 prostate cancer patients presenting at clinics or listed on the cancer registry in Newfoundland and Labrador and reviewed their charts. We compared the wait time (first visit to diagnosis) and the wait-related satisfaction for breast and prostate cancer patients who received regular screening tests and whose cancer was screening test–detected (“screen/screen”); who received regular screening tests and whose cancer was symptomatic (“screen/symptomatic”); who did not receive regular screening tests and whose cancer was screen test–detected (“no screen/screen”); and who did not receive regular screening tests and whose cancer was symptomatic (“no screen/symptomatic”).

Results

Although there were no group differences with respect to having a long wait (greater than the median of 47.5 days) for breast cancer patients (47.8% screen/screen, 54.7% screen/symptomatic, 50.0% no screen/ screen, 40.0% no screen/symptomatic; p = 0.814), a smaller proportion of the screen/symptomatic patients were satisfied with their wait (72.5% screen/ screen, 56.4% screen/symptomatic, 100% no screen/ screen, 90.9% no screen/symptomatic; p = 0.048).A larger proportion of screen/symptomatic prostate cancer patients had long waits (>104.5 days: 41.3% screen/screen, 92.0% screen/symptomatic, 46.0% no screen/screen, 40.0% no screen/symptomatic; p = 0.011) and a smaller proportion of screen/ symptomatic patients were satisfied with their wait (71.2% screen/screen, 30.8% screen/symptomatic, 76.9% no screen/screen, 90.9% no screen/symptomatic; p = 0.008).

Conclusions

Diagnosis-related wait times and satisfaction were poorest among patients who received regular screening tests but whose cancer was not detected by those tests.     

Low probability of disease cure in advanced ovarian carcinomas before the PARP inhibitor era

Background In ovarian carcinomas, the likelihood of disease cure following first-line medical-surgical treatment has been poorly addressed. The objective was to: (a) assess the likelihood of long-term disease-free (LDF) > 5 years; and (b) evaluate the impact of the tumour primary chemosensitivity (assessed with the modelled CA-125 KELIM) with respect to disease stage, and completeness of debulking surgery.Methods Three Phase III trial datasets (AGO-OVAR 9; AGO-OVAR 7; ICON-7) were retrospectively investigated in an “adjuvant dataset”, whilst the Netherlands Cancer Registry was used in a “neoadjuvant dataset”. The prognostic values of KELIM, disease stage and surgery outcomes regarding the likelihood of LDF were assessed using univariate/multivariate analyses.Results Of 2029 patients in the “adjuvant dataset”, 82 (4.0%) experienced LDF (Stage I–II: 25.9%; III: 2.1%; IV: 0.5%). Multivariate analyses identified disease stage and KELIM (OR = 4.24) as independent prognostic factors. Among the 1452 patients from the “neoadjuvant dataset”, 36 (2.4%) had LDF (Stage II–III: 3.3%; IV: 1.3%). Using multivariate tests, high-risk diseases (OR = 0.18) and KELIM (OR = 2.96) were significant.Conclusion The probability of LDF > 5 years after first-line treatment in 3486 patients (<4%) was lower than thought. These data could represent a reference for future studies meant to assess progress related to PARP inhibitors.Subject terms: Medical research, Ovarian cancer     

Adjuvant platinum-based chemotherapy in radically resected adrenocortical carcinoma: a cohort study

Background After radical resection, patients with adrenocortical carcinoma (ACC) frequently experience recurrence and, therefore, effective adjuvant treatment is urgently needed. The aim of the study was to investigate the role of adjuvant platinum-based therapy.Methods In this retrospective multicentre cohort study, we identified patients treated with adjuvant platinum-based chemotherapy after radical resection and compared them with patients without adjuvant chemotherapy. Recurrence-free and overall survival (RFS/OS) were investigated in a matched group analysis and by applying a propensity score matching using the full control cohort (n = 268). For both approaches, we accounted for immortal time bias.Results Of the 31 patients in the platinum cohort (R0 n = 25, RX n = 4, R1 n = 2; ENSAT Stage II n = 11, III n = 16, IV n = 4, median Ki67 30%, mitotane n = 28), 14 experienced recurrence compared to 29 of 31 matched controls (median RFS after the landmark at 3 months 17.3 vs. 7.3 months; adjusted HR 0.19 (95% CI 0.09–0.42; P < 0.001). Using propensity score matching, the HR for RFS was 0.45 (0.29–0.89, P = 0.021) and for OS 0.25 (0.09–0.69; P = 0.007).Conclusions Our study provides the first evidence that adjuvant platinum-based chemotherapy may be associated with prolonged recurrence-free and overall survival in patients with ACC and a very high risk for recurrence.Subject terms: Adrenal tumours, Chemotherapy     

Prognostic factors for relapse in stage I seminoma: a new nomogram derived from three consecutive,risk-adapted studies from the Spanish Germ Cell Cancer Group (SGCCG)

BackgroundWe aimed to analyze prognostic factors for relapse in stage I seminoma managed by either active surveillance or adjuvant chemotherapy, and to describe the long-term patterns of recurrence in both groups.Patients and methodsFrom 1994 to 2008, 744 patients were included in three consecutive, prospective risk-adapted studies by the Spanish Germ Cell Cancer Group. Low-risk patients were managed by surveillance and high-risk patients were given two courses of adjuvant carboplatin. Relapses were treated mainly with chemotherapy. Patient age, tumor size, histological variant, pT staging, rete testis invasion, and preoperative serum BHCG levels were assessed for prediction of disease-free survival (DFS).ResultsAfter a median follow-up of 80 months, 63 patients (11.1%) have relapsed: 51/396 (14.8%) on surveillance and 12/348 (3.2%) following adjuvant carboplatin. Actuarial overall 5-year DFS was 92.3% (88.3% for surveillance versus 96.8% for chemotherapy, P = 0.0001). Median time to relapse was 14 months. Most recurrences were located at retroperitoneum (86%), with a median tumor size of 26 mm. All patients were rendered disease-free with chemotherapy (92%), radiotherapy (5%), or surgery followed by chemotherapy (3%). A nomogram was developed from surveillance patients that includes two independent, predictive factors for relapse: rete testis invasion and tumor size (as a continuous variable).ConclusionLong-term follow-up confirms the risk-adapted approach as an effective option for patients with stage I seminoma. The pattern of relapses after adjuvant chemotherapy is similar to that observed following surveillance. A new nomogram for prediction of DFS among patients on surveillance is proposed. Rete testis invasion and tumor size should be taken into account when considering the administration of adjuvant carboplatin. Prospective validation is warranted.     

The evolving treatment paradigm of locally advanced rectal cancer: a narrative review

Background and ObjectiveSurgery is still considered the mainstay of treatment of locally advanced rectal cancer (LARC). Nevertheless, “curable” disease may still pose a great risk for both local and distant relapses. Since the early eighties of the past century, we have witnessed mounting evidence supporting the multi-modality approach to tackle this disease effectively. The multi-modality approach is variable between different positive trials. In this review, we discuss the treatment evolution of LARC, highlighting the key differences between the different contemporary strategies utilized. Based on current evidence, we sought to define distinct patient subgroups and to propose a treatment algorithm that best fits patient’s risk.MethodsWe conducted a literature search through PubMed and Google scholar. Eligible papers were phase 2/3 trials [in organ preservation (OP), observational and retrospective studies were also acceptable] published in English. We used keywords such as “locally advanced rectal cancer”, “perioperative therapy in rectal cancer”, “short course radiotherapy”, “chemoradiation in rectal cancer”, “interval to surgery”, “Neoadjuvant therapy”, “Organ preservation” and “Total neoadjuvant treatment [TNT]”.Key Content and FindingsVarious trials consistently demonstrated the benefit of preoperative radiotherapy in LARC, the role of adjuvant chemotherapy is controversial based on published studies, TNT was associated with a risk reduction in distant metastasis, and more reassuring evidence is accumulating regarding OP.ConclusionsThe treatment landscape of LARC is rapidly changing. Clinicians should carefully tailor treatment strategy based on patient’s risk.     

Optimal adjuvant chemotherapy completion time for stage III colon cancer: a cohort study

BackgroundAdjuvant chemotherapy for 6 months following surgery is the standard treatment plan for stage III colon cancer. The aim of the present study was to determine whether the adjuvant chemotherapy completion time for stage III colon cancer had an effect on prognosis and cut-off time that affected the prognosis.MethodsThis was a retrospective study of stage III colon cancer patients who completed adjuvant chemotherapy at Guangzhou Red Cross Hospital from January 2010 to December 2017. Univariate and multivariate analyses were used to determine the association between adjuvant chemotherapy completion time and the 3-year disease-free survival (DFS). The restricted cubic spline model was used to analyze the cut-off time that affected the 3-year DFS.ResultsA total of 431 patients were included in the study. The 3-year DFS was associated with a combination of obstruction or perforation, preoperative serum carcino-embryonic antigen (CEA) concentration, T stage, N stage, pathological stage, and adjuvant chemotherapy completion time in the univariate analysis (P<0.05). A combination of obstruction or perforation, preoperative serum CEA concentration, N stage, and adjuvant chemotherapy completion time were independent prognostic factors in the multivariate analysis (P<0.05). The cut-off time was 28 weeks for adjuvant chemotherapy completion time in the restricted cubic spline model analysis. For those whose adjuvant chemotherapy completion time was >28 weeks, the risk of 3-year recurrence was 1.428 times higher compared with those whose adjuvant chemotherapy completion time was ≤28 weeks. [P=0.032, 95% confidence interval (CI): 1.034–2.055].ConclusionsThe 3-year DFS of stage III colon cancer was related to the adjuvant chemotherapy completion time. For those who completed adjuvant chemotherapy >28 weeks, the risk of 3-year recurrence increased.     

Evaluation of tumour surveillance protocols and outcomes in von Hippel-Lindau disease in a national health service

Background Von Hippel-Lindau (VHL) disease is an inherited tumour predisposition syndrome and a paradigm for the importance of early diagnosis and surveillance. However, there is limited information on the “real world” management of VHL disease.Methods A national audit of VHL disease in the United Kingdom.Results VHL disease was managed mostly via specialist clinics coordinated through regional clinical genetics services (but frequently involving additional specialties). Over the study period, 19 genetic centres saw 842 individuals (393 males, 449 females) with a clinical and/or molecular diagnosis of VHL disease and 74 individuals (35 male, 39 female) with a prior risk of 50% (affected parent). All centres offered retinal, central nervous system and abdominal surveillance to affected individuals and at-risk relatives though surveillance details differed between centres (but complied with international recommendations). Renal lesions detected on the first surveillance scan were, on average, larger than those detected during subsequent scans and the larger the diameter at detection the greater the likelihood of early intervention.Conclusions In a state-funded health care system individuals with a rare inherited cancer predisposition syndrome are generally able to access appropriate surveillance and patient management is improved compared to historical data. The “real world” data from this study will inform the future development of VHL management protocols.Subject terms: Translational research, Risk factors, Urological cancer     

Multigene tests for breast cancer: the physician’s perspective

Breast cancer is the most common tumour in women and the first cause of death for cancer in the female population. Preserving the quality of life has therefore become an important objective in the management of the disease. The benefits of adjuvant chemotherapy in patients with HR+ HER2- early breast cancer should always be balanced against its potential short and long-term adverse effects, and identifying the appropriate patients for whom chemotherapy can offer the highest clinical benefit is critical. Besides clinical and pathological factors, today four multigene tests able to guide the choice of the adjuvant therapy early breast cancer are available in Italy: Oncotype DX^®, EndoPredict^®, MammaPrint^® e Prosigna^®. This review evaluates the main characteristics of these diagnostic tests, the studies on clinical utility, their economic impact and their inclusion in international and national guidelines. The Oncotype DX Breast Recurrence Score^® test is the only multigene test validated, with level IA evidence, to guide the adjuvant therapy decisions: hormone therapy alone for most patients with RS results 0–25, and chemotherapy for patients with RS results 26–100. Clinical data demonstrate that the Oncotype DX test is able to significantly impact therapeutic decisions, reducing chemotherapy use up to 49% and supporting the use of chemotherapy (up to 12%) in potentially under-treated patients. Based on the level of clinical evidence and established clinical utility, several multigene tests have been included in the main international guidelines, with recommendations ranging from “strong” to “moderate”.     

Recommendations from the European Commission Initiative on Breast Cancer for multigene testing to guide the use of adjuvant chemotherapy in patients with early breast cancer,hormone receptor positive,HER-2 negative

Background Predicting the risk of recurrence and response to chemotherapy in women with early breast cancer is crucial to optimise adjuvant treatment. Despite the common practice of using multigene tests to predict recurrence, existing recommendations are inconsistent. Our aim was to formulate healthcare recommendations for the question “Should multigene tests be used in women who have early invasive breast cancer, hormone receptor-positive, HER2-negative, to guide the use of adjuvant chemotherapy?”Methods The European Commission Initiative on Breast Cancer (ECIBC) Guidelines Development Group (GDG), a multidisciplinary guideline panel including experts and three patients, developed recommendations informed by systematic reviews of the evidence. Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision frameworks were used. Four multigene tests were evaluated: the 21-gene recurrence score (21-RS), the 70-gene signature (70-GS), the PAM50 risk of recurrence score (PAM50-RORS), and the 12-gene molecular score (12-MS).Results Five studies (2 marker-based design RCTs, two treatment interaction design RCTs and 1 pooled individual data analysis from observational studies) were included; no eligible studies on PAM50-RORS or 12-MS were identified and the GDG did not formulate recommendations for these tests.Conclusions The ECIBC GDG suggests the use of the 21-RS for lymph node-negative women (conditional recommendation, very low certainty of evidence), recognising that benefits are probably larger in women at high risk of recurrence based on clinical characteristics. The ECIBC GDG suggests the use of the 70-GS for women at high clinical risk (conditional recommendation, low certainty of evidence), and recommends not using 70-GS in women at low clinical risk (strong recommendation, low certainty of evidence).Subject terms: Prognostic markers, Breast cancer     

CIRCULATE‐Japan: Circulating tumor DNA–guided adaptive platform trials to refine adjuvant therapy for colorectal cancer

Adjuvant chemotherapy has reduced the risk of tumor recurrence and improved survival in patients with resected colorectal cancer. Potential utility of circulating tumor DNA (ctDNA) prior to and post surgery has been reported across various solid tumors. We initiated a new type of adaptive platform trials to evaluate the clinical benefits of ctDNA analysis and refine precision adjuvant therapy for resectable colorectal cancer, named CIRCULATE‐Japan including three clinical trials. The GALAXY study is a prospectively conducted large‐scale registry designed to monitor ctDNA for patients with clinical stage II to IV or recurrent colorectal cancer who can undergo complete surgical resection. The VEGA trial is a randomized phase III study designed to test whether postoperative surgery alone is noninferior to the standard therapy with capecitabine plus oxaliplatin for 3 months in patients with high‐risk stage II or low‐risk stage III colon cancer if ctDNA status is negative at week 4 after curative surgery in the GALAXY study. The ALTAIR trial is a double‐blind, phase III study designed to establish the superiority of trifluridine/tipiracil as compared with placebo in patients with resected colorectal cancer who show circulating tumor–positive status in the GALAXY study. Therefore, CIRCULATE‐Japan encompasses both “de‐escalation” and “escalation” trials for ctDNA‐negative and ‐positive patients, respectively, and helps to answer whether measuring ctDNA postoperatively has prognostic and/or predictive value. Our ctDNA‐guided adaptive platform trials will accelerate clinical development toward further precision oncology in the field of adjuvant therapy. Analysis of ctDNA status could be utilized as a predictor of risk stratification for recurrence and to monitor the effectiveness of adjuvant chemotherapy. ctDNA is a promising, noninvasive tumor biomarker that can aid in tumor monitoring throughout disease management.     

Controversial Issues Regarding Obligatory Adjuvant Chemotherapy for Stage IIIA Colon Cancer

PurposeTo investigate the survival outcomes of patients with stage IIIA colon cancer. In addition, risk factors that affect the oncologic outcome of stage IIIA colon cancer patients and the role of adjuvant chemotherapy were evaluated.Patients and MethodsData from 326 colon cancer patients with stage IIIA who underwent surgery between January 2000 and December 2016 were retrospectively reviewed. Patients diagnosed with hereditary cancer and those who received preoperative neoadjuvant therapy were excluded.ResultsThe 5-year recurrence-free survival (RFS) rate in stage IIIA colon cancer patients who underwent curative resection was 93.9%. Of the patients with recurrence, the survival rate of those who underwent surgical resection was better than that of patients who received palliative chemotherapy or no treatment (12/13, 92.3% vs. 2/4, 50.0%), respectively; P = .052). Multivariate analysis showed that high serum carcinoembryonic antigen (s-CEA) was an independent and statistically significant prognostic factor for RFS, and ulcerative gross-type disease tended to be a poor prognostic factor. There was no difference in RFS in patients with elevated s-CEA or ulcerative gross-type disease according to receipt of adjuvant chemotherapy.ConclusionPatients with stage IIIA colon cancer had a relatively favorable survival outcome. Even in patients with relapsed disease, long-term survival could be a result if surgical resection is accomplished. High s-CEA concentration is a significant poor prognostic factor for recurrence, and ulcerative gross-type disease tends to be a poor prognostic factor. Postoperative adjuvant chemotherapy may not provide a survival benefit for stage IIIA colon cancer, even in the presence of risk factors. Because of the rarity of this patient group and the low rate of recurrence, large-scale multicenter studies are needed to find and confirm the risk group that would receive a benefit from adjuvant chemotherapy.     

The “Sandwich” Schedule: A Well-Tolerated Adjuvant Treatment Both in Intermediate–High- and High-Risk Endometrial Cancer

(1) Background: In intermediate–high- and high-risk endometrial cancer (EC), radiotherapy (RT) and chemotherapy (CT) play a basic role. However, there is controversy regarding the optimal timing of their combination. The “sandwich” schedule involves adjuvant CT followed by RT and subsequent CT. The aim of this study is to assess the tolerability and efficacy of the “sandwich” schedule. (2) Methods: A retrospective study was conducted in two gynecological oncology units in Torino, Italy, from 1 January 2003 until 31 December 2021. Intermediate–high- and high-risk patients with available clinical data were included. Compliance with treatment, CT and RT toxicities, disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed. (3) Results: A total of 118 patients were selected: 27.1% FIGO I-II stages and 72.9% III-IV. Most of the patients (75.4%) received a carboplatin–paclitaxel combination, and as much as 94.9% of CT cycles were completed. Chemotherapy-related G3-4 toxicities were detected in 5.3% of the patients, almost half of which were hematological. Grade 2 gastrointestinal and genitourinary toxicities were reported in 8.4% and 4.2% of cases, respectively. With a median follow-up of 46 months, DFS was 77.6%, CSS was 70% and 5-year OS was 54%. (4) Conclusions: The “sandwich” schedule for CT and RT combination is an effective adjuvant treatment with low toxicity both in intermediate–high- and high-risk EC.     

Persistent neuropathy among early-stage breast cancer survivors in a population-based cohort

Background The prevalence of persistent peripheral neuropathy (PN) in early-stage breast cancer (ESBC) survivors is largely unknown. We explored the occurrence and risk factors of PN among long-term ESBC survivors treated with taxane chemotherapy.Methods A population-based cohort of 884 recurrence-free ESBC survivors diagnosed 2010–2015 in the South East Health Care region, Sweden and 1768 control women without prior cancer received a postal questionnaire that included the European Organisation for Research and Treatment of Cancer chemotherapy-induced peripheral neuropathy (CIPN20) items. Prevalence, relative risks (RRs) (Poisson regression) and risk factors (binomial regression) were calculated. Adjustments were made for confounding factors (e.g. age, body mass index, comorbidities).Results The response rate was 79% for survivors and 59% for controls. The median time post taxane was 3.6 years (1.5–7.3 years). The adjusted RR was highest (RR 1.8) for “tingling/numbness of toes/feet”. Individual sensory symptoms occurred in 8.9–48.4% and motor symptoms in 7.2–61.3% of survivors; the most prevalent symptoms were “difficulty opening jar” and “cramps in feet”. Paclitaxel, older age, overweight, diabetes mellitus, vibrating hand tools, autoimmune disease and smoking were independent risk factors.Conclusions PN was more common among ESBC survivors than control women and many symptoms persisted over time. Risk factors should be considered when treatment decisions are made.Subject terms: Breast cancer, Chemotherapy