Sequential Adjuvant Chemotherapy Research Articles

Idiopathic Intracranial Hypertension in a Breast Cancer Patient Receiving Adjuvant Paclitaxel: A Case Report and a Review of the Liter

Background: Paclitaxel is a cytotoxic drug belonging to the taxane family, widely used in medical oncology, such as in breast cancer, in which it has demonstrated great efficacy, whether as metastatic or adjuvant treatment. Paclitaxel's main toxicities are immediate anaphylactic reactions and peripheral neuropathy. The occurrence of idiopathic intracranial hypertension is an unusual event.  The Clinical Case: This is a 53-year-old Moroccan woman, treated for breast cancer; she was put on sequential adjuvant chemotherapy after surgery. She received 3 courses of Doxorubicin and Cyclophosphamide without incident and then we started weekly Paclitaxel. From the very first courses, the patient presented with continuous but moderate headaches, and a cerebral Magnetic Resonance Imaging (MRI) showed signs of idiopathic intracranial hypertension, which was confirmed and treated in the neurology department. The patient progressed well, allowing the 12 courses of paclitaxel to be continued.  Conclusion: Idiopathic intracranial hypertension is an unusual complication of paclitaxel. The occurrence of headache or other neurological symptoms in a patient being treated for breast cancer requires an urgent brain MRI, particularly to look for brain metastases.

Long-Term Quality of Life after Adjuvant Sequential Chemotherapy and/or Radiotherapy in Endometrial Cancer Survivors

Long-Term Quality of Life after Adjuvant Sequential Chemotherapy and/or Radiotherapy in Endometrial Cancer Survivors

PO-1433 Outcomes after adjuvant sequential chemotherapy and radiotherapy for high-risk endometrial cancer

PO-1433 Outcomes after adjuvant sequential chemotherapy and radiotherapy for high-risk endometrial cancer

Impact of the adjuvant management and risk factors on survival in FIGO stage 3 endometrial cancer patients.

Patients with FIGO stage III endometrial cancer routinely receive adjuvant therapy. The purpose of this study was to evaluate overall survival (OS) and disease-free survival (DFS) in patients with stage IIIA to IIIC2 patients by treatment modality received and risk factors. Patients with stage III endometrial cancer treated from 2000-2010 were identified in the provincial cancer registry. Clinicopathologic characteristics, adjuvant treatments and outcomes were compared using descriptive and multivariable analyses. 261 patients had stage 3 endometrial cancer, 132 with stage IIIA, 9 with IIIB, 85 with IIIC1 and 35 with IIIC2. 39 had FIGO grade 1 disease; 73, grade 2; 147, grade 3. 160 had endometrioid and 35 had serous carcinoma. 161 patients received sequential adjuvant chemotherapy (CT) and radiotherapy (RT); 33 received RT only; 32 received CT only; 35 received neither. 5-year (5Y) DFS and OS were similar among stage IIIA (DFS 46.7%, OS 58.5%), IIIB (DFS 50.8%, OS 58.5%), IIIC1 (DFS 44%, OS 49.9%) and IIIC2 (DFS 42%, OS 41.6%). Use of adjuvant RT was associated with improved median DFS (53.7 vs 14.7m, p<0.00001) and OS (61.9 vs 25.7m, p<0.00001) compared to no RT. Likewise, use of adjuvant CT was also associated with improved DFS (54.8 vs 16.5m, p<0.00001) and OS (62.9 vs 26.5m, p<0.00001) compared to no CT. Those who received both chemotherapy and radiotherapy had better outcomes with 5-year DFS (58.3%) and OS (65.2%), compared with those who received monotherapy. On multivariate analysis, grade 3 disease, deep myometrial invasion >50%, and no adjuvant RT or CT were identified as adversely impacting DFS and OS. In stage III endometrial cancer patients, use of both chemotherapy and radiation therapy was associated with improved DFS and OS and therefore should be recommended in all eligible patients after resection.

The Effects of Different Induction Chemotherapy Cycles and Adjuvant Chemotherapy on the Survival Outcomes of Patients With Locally Advanced Nasopharyngeal Carcinoma

ObjectiveThis study investigated whether differences in the induction chemotherapy (IC) cycle number and adjuvant chemotherapy (AC) affect survival outcomes in patients with locally advanced nasopharyngeal carcinoma (LA-NPC).MethodsThe survival outcomes of 386 consecutive LA-NPC patients treated between January 2015 and March 2018 were retrospectively analyzed. Univariate and multivariate analyses were used to compare treatment groups defined by IC< 3 or ≥3 IC cycles followed by radiotherapy with or without AC (i.e., IC<3+AC, IC<3+non-AC, IC≥3+AC, and IC≥3+non-AC groups).ResultsThe median follow-up time was 53 months (range: 2-74 months) and the median number of IC cycles was 2 (range: 1-6 cycles). The 3-year overall survival (OS) rate was significantly higher in patients with IC≥3 cycles compared to IC<3 cycles (95.7% vs. 90.3%, P=0.020). Multivariate analysis indicated that the IC cycle number is an independent factor for OS (hazard ratio=0.326, P=0.007). Furthermore, patients in the IC<3+AC group had a better OS rate than those in the IC<3+non-AC group (91.6% vs. 79.1%, P=0.030), indicating that AC positively affected OS in patients with IC<3. However, no significant difference in the OS rate was found between IC≥3+non-AC and IC≥3+AC groups (92.1% vs. 94.6%, P =0.550).ConclusionThe IC cycle number appears to be an independent prognostic factor for higher OS in LA-NPC patients who received ≥3 cycles. Sequential AC after IC plus radiotherapy may improve OS in patients with IC<3 cycles.

Dose-dense sequential adjuvant chemotherapy in the trastuzumab era: final long-term results of the Hellenic Cooperative Oncology Group Phase III HE10/05 Trial.

Dose-dense sequential chemotherapy with anthracyclines and taxanes achieved an 18% reduction of recurrence risk in early breast cancer (BC). The optimal chemotherapy schedule and interval between cycles remain under investigation. Overall, 990 patients were randomised to receive either three cycles of epirubicin (E, 110 mg/m2) every 2 weeks followed by 3 cycles of paclitaxel (T, 200 mg/m2) every 2 weeks followed by three cycles of intensified CMF (Control Arm A, E-T-CMF) that was previously used in BC or three cycles of epirubicin followed by three cycles of CMF followed by nine consecutive weekly cycles of docetaxel (wD) 35 mg/m2 (Arm B, E-CMF-wD) or nine consecutive weekly cycles of paclitaxel (wT) 80 mg/m2 (Arm C, E-CMF-wT). Trastuzumab was administered for HER2-positive disease. At a median follow-up of 13.3 years, 330 disease-free survival (DFS) events (33.3%) were reported. DFS and overall survival (OS) did not differ between patients in the combined B and C arms versus arm A either in the entire cohort (HR = 0.90, P = 0.38 and HR = 0.85, P = 0.20) or among trastuzumab-treated patients (HR = 0.69, P = 0.13 and HR = 0.67, P = 0.13). Thirty-four patients (3.4%) developed secondary neoplasms. Overall, no significant differences in survival were found amongst the studied regimens after a long-term observational period. Australian New Zealand Clinical Trials Registry ACTRN12610000151033.

Prolonged Survival Following Treatment of Histiocytic Sarcoma of the Canine Urinary Bladder.

A 9 yr old castrated male miniature schnauzer was diagnosed histopathologically with a mucosal histiocytic sarcoma of the urinary bladder apex, biopsied at the time of surgical cystotomy. Sequential adjuvant chemotherapy, including both lomustine (discontinued because of adverse effects) and then doxorubicin, were employed. A response to both agents was documented. Ultimately, a complete response was achieved following completion of the doxorubicin protocol. A complete response persisted 768 days following diagnosis at last follow-up. Histiocytic sarcoma of the urinary bladder remains a rare diagnosis in veterinary medicine. Only one previous case report is currently published. This case contrasts with the previous case report, which reported a survival of only 2 mo.

Abstract P1-12-01: Dose-dense sequential adjuvant chemotherapy in the trastuzumab era: Final long-term results of the hellenic cooperative oncology group phase III HE10/05 trial

Abstract Background: Dose-dense sequential chemotherapy based on anthracyclines and taxanes has achieved an 18% reduction of recurrence risk in the adjuvant setting of early breast cancer (BC). However, the optimal chemotherapy schedule and the preferable interval between cycles are still under investigation. Methods: A total of 990 eligible BC patients were randomized to receive either 3 cycles of epirubicin (E,110 mg/m2) every 2 weeks followed by 3 cycles of paclitaxel (T, 200 mg/m2) every 2 weeks followed by 3 cycles of intensified CMF (Control Arm A, E-T-CMF; 333 patients) or three cycles of epirubicin followed by 3 cycles of CMF followed by 9 consecutive weekly cycles of docetaxel (wD) 35 mg/m2 (Experimental Arm B, E-CMF-wD; 331) or 9 consecutive weekly cycles of paclitaxel (wT) 80 mg/m2 (Experimental Arm C, E-CMF-wT; 326). Trastuzumab was administered for HER2-positive disease. The primary endpoint was disease-free survival (DFS). Results: At a median follow-up of 13.3 years, 330 DFS events (33.3%) had been reported. DFS and overall survival (OS) did not differ between patients in the combined B and C arms versus control arm A either in the entire cohort (HR=0.90, p=0.38 and HR=0.85, p=0.20) or among HER2-positive, trastuzumab-treated patients (HR=0.69, p=0.13 and HR=0.67, p=0.13). Thirty-four patients (3.4%) developed secondary neoplasms. Conclusions: Overall, no significant differences in DFS or OS were found amongst the studied regimens after a long-term observational period. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12610000151033 Citation Format: Flora Zagouri, Georgia-Angeliki Koliou, Foteinos Dimitrakopoulos, Christos Papadimitriou, Ioannis Binas, Angelos Koutras, Pavlos Papakostas, Christos Markopoulos, Vasileios Venizelos, Grigorios Xepapadakis, Charisios Karanikiotis, Amanda Psyrri, Dimitrios Bafaloukos, Paris Kosmidis, Gerasimos Aravantinos, Eleni Res, Davide Mauri, Anna Koumarianou, Kalliopi Petraki, Anna Tsipoura, Dimitrios Pectasides, Helen Gogas, George Fountzilas. Dose-dense sequential adjuvant chemotherapy in the trastuzumab era: Final long-term results of the hellenic cooperative oncology group phase III HE10/05 trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-12-01.

Sequential vs concurrent adjuvant chemotherapy of anthracycline and taxane for operable breast cancer

BackgroundWhether a sequential or concurrent regimen of anthracyclines and taxanes is superior for breast cancer is controversial. We compared the efficacy of two regimens in patients with operable breast cancer based on all relevant published data of phase III randomized controlled trials.MethodsA comprehensive literature search on PubMed, Web of Science, Embase, ScienceDirect, Google Scholar, and ClinicalTrials.gov databases was performed up to May 2020. Meta-analysis was performed to evaluate the different efficacy on disease-free survival (DFS) and overall survival (OS) for the two chemotherapy regimens. Subgroup analyses were further carried out in terms of node status and anthracycline selection.ResultsCompared to the concurrent regimen, the sequential regimen did not improve the DFS or OS in the population studied. Subgroup analysis showed that in node-positive patients, the sequential regimen had better DFS, but not OS, than the concurrent regimen. In sequential regimen, patients who received doxorubicin and taxanes had improved DFS and OS than patients who were administered epirubicin and taxanes. Furthermore, for patients who received doxorubicin and taxanes, compared to the sequential regimen, fewer cycles (4 cycles) of concurrent treatment resulted in a worse DFS and OS, which can be rescued by more cycles (6 cycles).ConclusionsThe sequential regimen of anthracyclines and taxanes for patients with operable breast cancer did not yield a significant benefit in DFS or OS over the concurrent regimen. The sequential regimen, however, provided a better DFS than concurrent regimen for node-positive patients. Interestingly, further subgroup analysis showed that for node-positive patients who were given doxorubicin and taxanes, more cycles (6 cycles) of the concurrent regimen may rescue the efficacy for fewer cycles (4 cycles).

5-Fu-Based Doublet Regimen in Patients Receiving Perioperative or Postoperative Chemotherapy for Locally Advanced Gastric Cancer: When to Start and How Long Should the Regimen Last?

BackgroundThe duration and the optimal time to adjuvant chemotherapy (TAC) in locally advanced gastric cancer (LAGC) have net not been sufficiently demonstrated. Sequential adjuvant chemotherapy (AC) after neoadjuvant chemotherapy plus gastrectomy is increasingly utilized, making the question more complicated.Patients and MethodsData were collected from patients with LAGC who underwent 5-Fu-based doublet regimens as adjuvant treatment after gastrectomy in a single-center database. TAC and duration (cycles) were used to evaluate survival outcomes.ResultsA total of 816 patients were included. Patients received over six cycles and TAC less than 42 days significantly correlated with better survival (log-rank Ptrend<0.001). The analysis of TAC and number cycles were separately applied in perioperative chemotherapy (PEC) and postoperative chemotherapy (POC) group using Cox regression. The number of cycles revealed a statistical significance improving OS rate both in POC (HR=0.904, 95% CI=0.836–0.977, P=0.011) and PEC (HR=0.887, 95% CI=0.798–0.986, P=0.026), while only in POC did the TAC show an increasing trend of risk with borderline significance (OS: HR=1.008, 95% CI=0.999–1.018, P=0.094; PFS: HR=1.009, 95% CI=1.000–1.018, P=0.055). A spline model demonstrates the less improvement in survival after cycles of chemotherapy reaching six.ConclusionOur findings suggest that TAC is more likely to downregulate the survival benefit in POC rather than PEC, while overall survival is susceptible to cumulative cycles of chemotherapy in both groups. Furthermore, six cycles of chemotherapy tended to reach the maximum survival benefits. Prospective confirmation is required.

Clinical Outcomes and Prognostic Factors in Gastric Carcinoma Patients with Curative Surgery Followed by Adjuvant Treatment: Real-World Scenario.

A wide range of adjuvant treatment regimens exist in gastric carcinoma patients which include chemotherapy, radiotherapy, and/or both either sequential or concurrent. The study aimed to assess the benefit of adjuvant sequential chemotherapy followed by radiotherapy for operable gastric cancers and evaluatetheprognostic factors associated with clinical outcomes. Patients of stage IB-III gastric carcinoma who underwent radical surgery followed by adjuvant treatment from January 2013 to December 2016 were analyzed retrospectively. Survival was computed using Kaplan-Meier method and prognostic factors were analyzed in multivariate analysis using Cox progression hazard model. A P value < 0.05 was taken as statistically significant. A total of 108 patients were identified with a median follow-up of 31.7months (range: 6-96). Seventy-two percent of the patients received adjuvant sequential chemoradiation (N = 77) and 28% of patients received chemotherapy alone. The median survival was 26months (95% CI: 23.09-28.90). Overall survival (OS) rates for 1, 2, 3, 4, and 5years were 88.9%, 57.4%, 40.7%, 28.8%, and 20.4%, respectively. Five-year OS for stage-IB, II, and III was 75%, 45%, and 8.3%, respectively (p = 0.023). Surgical margin positivity (9.5% vs. 26.9%, p = 0.042), signet-ring cell histology (6.5% vs. 25.8%, p = 0.00), and adjuvant sequential chemoradiation (p = 0.002) showed a significant impact on survival outcomes and proved as independent prognostic factors. The present study demonstrated that survival in gastric carcinoma is influenced by the stage of disease and surgical margins. In locally advanced patients, radical surgery followed by sequential chemoradiation based on a doublet/triplet regimen was an independent prognostic factor for survival. Majority of patients in our set-up presented in locally advanced stage, curative resection followed by adjuvant sequential chemoradiation was an independent prognostic factor for survival.

84P Actual 5-year survival of dose-dense sequential adjuvant chemotherapy in early breast cancer (BC) patients treated in the post-trastuzumab era: A pooled analysis of 3 clinical trials

The addition of trastuzumab (T) in dose-dense (dd) sequential (s) chemotherapy (CT) has been found to improve the outcome of patients (pts) with HER2(+) BC. We aimed to evaluate the 5-year survival benefit of dds-CT in pts treated in the post-trastuzumab era. We analyzed 3,026 pts diagnosed with operable BC between 2005 and 2013, treated with dds-CT within one randomized and two observational HeCOG trials. Pts with HER2(+) disease had received T for 1 year. Hormonal and radiation therapy were administered, as indicated.The primary endpoints were disease-free survival (DFS) and overall survival (OS). In total, 59.7% of pts had Hormone receptor (HR)(+)/HER2(-)(luminal) tumors, 25.5% had HER2(+) disease, and 14.5% had triple-negative breast cancer (TNBC). T was administered in 95.5% of pts with HER2(+) disease. At a median follow-up of 7.4 years, the 5-year DFS rate of pts with HER2(+) and luminal tumors was 88%, respectively, as compared to 83% for those with TNBC. The 5-year OS rate was 93% for pts with HER2(+) disease, 92% for luminal and 87% for TNBC. Pts with luminal disease had the greatest 5-year DFS rates both among women with positive and negative nodes (86% and 95%, respectively), followed by pts with HER2(+) BC (83% and 94%, respectively) and TNBC (76% and 89%, respectively).The 5-year OS rate of pts with HER2(+) and luminal disease was 91%, respectively among pts with positive nodes and 97%, respectively in pts with node-negative BC. The 5-year OS rate of TNBC pts with node-negative disease was 92%. Trastuzumab is a part of one of success stories in Oncology, as its use dramatically improved the prognosis of HER2(+) pts. In this study, the outcomes of pts with HER2(+) BC were similar to those with luminal tumors, while TNBC remained the most unfavorable group.

Application of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for the prevention of neutropenia in triple negative breast cancer patients older than 65 years during adjuvant chemotherapy

Abstract Objective The aim of this study was to compare the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) for the prevention of neutropenia in elderly breast cancer patients during adjuvant chemotherapy. Methods A total of 45 oncology inpatients with breast cancer, who received adjuvant chemotherapy and were older than 65 years from May 2017 to October 2018 in the General Hospital of the Northern Theater of the Chinese people's Liberation Army, were included. Epirubivin Cyclophoshamide-Docetaxel (EC-T) sequential adjuvant chemotherapy was chosen. Forty-five patients were randomly divided into two groups; 25 patients in the treatment group were treated with PEG-rhG-CSF and 20 patients in the control group were not treated with PEG-rhG-CSF, but only rhG-CSF. The experimental group was treated with the PEG-rhG-CSF at the end of chemotherapy for 24-48 h, with a 6 mg subcutaneous injection once per chemotherapy cycle. In the control group, rhG-CSF was administered after 48 h of chemotherapy, with a 100 µg subcutaneous injection, 1/d, d 1-7. The dosage could be increased step by step with the exacerbation of neutropenia. The primary aims of this study was to discover the incidence of leukopenia, neutropenia, neutrophilic fever, and adverse reactions in the two groups. Results The incidence of neutropenia, neutrophilic fever and adverse reactions decreased in the treatment group compared to the control group, but no significant difference existed between two groups (P &gt; 0.05). Patients in treatment group had a lower, but not statistically significant, incidence of adverse reactions (P &gt; 0.05). Conclusion Applying PEG-rhG-CSF could be effective in preventing neutropenia in elderly patients with postoperative adjuvant chemotherapy to treat breast cancer. It may effectively control the occurrence of neutropenia after chemotherapy and reduce the chance of infection. The incidence of side effects, such as fever and bone pain, was low. The adverse drug reactions were well tolerated by patients, which could ensure the smooth progress of chemotherapy.

Sequential Adjuvant Chemotherapy and Radiation is Associated with Improved Overall Survival Compared to Initial Concurrent Adjuvant Chemoradiation in Stage III Endometrial Cancer

Sequential Adjuvant Chemotherapy and Radiation is Associated with Improved Overall Survival Compared to Initial Concurrent Adjuvant Chemoradiation in Stage III Endometrial Cancer

Clinical Significance of Lymph-Node Ratio in Determining Supraclavicular Lymph-Node Radiation Therapy in pN1 Breast Cancer Patients Who Received Breast-Conserving Treatment (KROG 14-18): A Multicenter Study.

This study evaluated the clinical significance of the lymph-node ratio (LNR) and its usefulness as an indicator of supraclavicular lymph-node radiation therapy (SCNRT) in pN1 breast cancer patients with disease-free survival (DFS) outcomes. We retrospectively analyzed the clinical data of patients with pN1 breast cancer who underwent partial mastectomy and taxane-based sequential adjuvant chemotherapy with postoperative radiation therapy in 12 hospitals (n = 1121). We compared their DFS according to LNR, with a cut-off value of 0.10. The median follow-up period was 66 months (range, 3–112). Treatment failed in 73 patients (6.5%) and there was no significant difference in DFS between the SCNRT group and non-SCNRT group. High LNR (>0.10) showed significantly worse DFS in both univariate and multivariate analyses (0.010 and 0.033, respectively). In a subgroup analysis, the effect of SCNRT on DFS differed significantly among patients with LNR > 0.10 (p = 0.013). High LNR can be used as an independent prognostic factor for pN1 breast cancer patients treated with partial mastectomy and postoperative radiotherapy. It may also be useful in deciding whether to perform SCNRT to improve DFS.

Randomized phase III trial of adjuvant sequential chemotherapy plus radiotherapy versus adjuvant radiotherapy alone for locally advanced bladder cancer after radical cystectomy: Urothelial carcinoma subgroup analysis.

351 Background: The role of post-operative chemotherapy after radical cystectomy (RC) is not well-defined. While some retrospective studies have shown a benefit, trials have been under-powered. In a phase III Egyptian trial, we evaluated the benefit of adjuvant chemo in locally advanced bladder cancer (LABC) patients treated with post-operative radiotherapy (PORT). In this study, we report a post-hoc subgroup analysis of patients with urothelial histology. We hypothesized that the addition of adjuvant chemo would improve disease-free survival (DFS) compared to PORT alone for LABC. Methods: A randomized phase III trial was opened to compare PORT vs. sequential chemo+PORT after RC for LABC &amp; accrued from 2002–2008 at the NCI in Cairo. Bladder cancer pts ≤70 with at least one of the following factors (≥pT3b, grade 3, positive nodes) with negative margins after RC plus pelvic node dissection were eligible. RT was delivered using 3-D conformal RT to the pelvis to 45Gy in 1.5Gy BID. Chemo+PORT included 2 cycles of gemcitabine/cisplatin before &amp; after RT. The primary endpoint was DFS. Secondary endpoints included overall survival (OS) &amp; late GI toxicity. Results: 153 pts were enrolled. 53% had urothelial carcinoma (41 chemo+PORT &amp; 40 PORT). In the urothelial cohort, the arms were well-balanced. Median age was 55. Median follow-up was 21 months for chemo+PORT (range 4-127) &amp; 15 months for PORT (range 5-70). There were 2 local failures for PORT &amp; none for chemo+PORT. Two-year DFS for chemo+PORT vs. PORT was 62% (95% CI 53-71%) &amp; 48% (95% CI 39-58%), log-rank p=0.031. Two-year OS was 71% (95% CI 63-80%) &amp; 51% (95% CI 40-61%), log-rank p=0.048. On multivariable analysis, chemo+PORT was a significant predictor of improved DFS (HR 0.42 95% CI 0.21-0.85, p=0.016) and OS (HR 0.45, 95% CI 0.21-0.96, p=0.039). In the entire cohort, late grade ≥3 GI toxicity was observed in 5 chemo+PORT patients (7%) &amp; 6 PORT patients (8%). Conclusions: The addition of adjuvant chemo to PORT improved DFS &amp; OS for LABC after RC with acceptable late GI toxicity. The results suggest a role for adjuvant therapies to address both local &amp; distant disease. Clinical trial information: 01734798.

Abstract P4-08-13: Prognostic significance of CD8+ tumor-infiltrating lymphocytes (TILs) in patients with early breast cancer (EBC) treated with dose-dense sequential adjuvant chemotherapy (dds-CT). An observational study (ACTRN12616001043426)

Abstract Background - aim: Information on the prognostic role of cytotoxic CD8+ T cells in the era of modern adjuvant CT is limited. The primary objective of the present report is to assess the prognostic impact of CD8+ cells in patients with intermediate or high-risk EBC (T1-3N1-2M0) treated with dds-CT. Secondary endpoints are safety, disease-free survival (DFS) and overall survival (OS). Patients and Methods: Patients (N=1,000) were treated with 4 cycles of Epirubicin, 75mg/m2, and Cyclophophamide, 600mg/m2 every 2 weeks followed by 4 cycles of Docetaxel (D), 100mg/m2 every 3 weeks with G-CSF support in all cycles. Trastuzumab was initiated concurrently with D and continued for a total of 1 year. Hormonal and radiation therapy were given post CT, as indicated. Formalin-fixed paraffin-embedded tumors were available for 642 patients (64.2%) and were centrally assessed for immunohistochemical subtypes (IHC4; N=526), stromal TILs density by morphology (N=636), as well as stromal and intratumoral cytotoxic CD8+ T cell numbers (N=554). TILs and CD8+ were assessed as continuous variables for associations and as 10% increments for outcome. Results: In total, 901/1,000 pts (90.1%) completed 8 cycles of CT. Severe (gradeIII-IV) toxicitiesincludedneutropenia (5.6%), leucopenia (3.6%), lymphopenia (2.1%), hand-footsyndrome (2.1%), and hepatotoxicity (1.8%). Febrileneutropenia occurred in 1.6% of the patients. The 5-year DFS and OS rates were 89.5% and 93.1%, respectively. Luminal A tumors were classified in 26.2%, Luminal B in 35.2%, luminal HER2 in 9.5%; HER2-enriched in 7.2%; and, triple-negative (TNBC) in 21.9% of informative patients. Among subtypes, stromal TILs density was higher in HER2-enriched and TNBC (p&amp;lt;0.001); intratumoral CD8+ values were higher in TNBC (p&amp;lt;0.001); and, stromal CD8+ were higher in HER2-enriched (p=0.034). In all patients, TILs density and intratumoral CD8+ cell numbers were not associated with DFS and OS, while increased stromal CD8+ were marginally associated with prolonged DFS (HR=0.98, 95%CI 0.96-1.00, p=0.066).Adjusted for histological grade, menopausal, ER/PgR and nodal status, higher stromal CD8+ were associated with prolonged DFS (HR=0.98, 95% CI 0.96-1.00, p=0.043). In TNBC, higher stromal TILs density conferred prolonged DFS (HR=0.97, 95%CI 0.94-0.99, p=0.029), which retained its prognostic significance in multivariate analysis (HR=0.97, 95% CI 0.94-1.00, p=0.049). Conclusions: In this study, dds-CT was well tolerated and active in patients with EBC. We confirm the presence of morphologically assessed higher TILs density, and of higher cytotoxic CD8+ T cell numbers in hormone receptor negative EBC, as well as the favorable prognostic impact of higher stromal TILs density in TNBC. In comparison to stromal TILs density, higher stromal CD8+ may confer favorable prognosis irrespectively of EBC subtype. Stromal CD8+ seems to be a marker worth further standardizing for reporting on immune cell infiltrates in EBC. Citation Format: Kourea HP, Koletsa T, Kotoula V, Koliou G-A, Batistatou A, Pentheroudakis G, Arapantoni-Dadioti P, Zagouri F, Bobos M, Sotiropoulou M, Papoudou-Bai A, Chrisafi S, Efstratiou I, Aravantinos G, Nicolaou I, Gogas H, Visvikis A, Christodoulou C, Petraki C, Koutras A, Psyrri A, Pectasides D, Fountzilas G. Prognostic significance of CD8+ tumor-infiltrating lymphocytes (TILs) in patients with early breast cancer (EBC) treated with dose-dense sequential adjuvant chemotherapy (dds-CT). An observational study (ACTRN12616001043426) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-13.

A multi-institutional analysis of sequential versus 'sandwich' adjuvant chemotherapy and radiotherapy for stage IIIC endometrial carcinoma.

ObjectiveTo analyze the outcomes of sequential or sandwich chemotherapy (ChT) and radiotherapy (RT) in patients with node-positive endometrial cancer (EC).MethodsData from 4 centers were collected retrospectively for 179 patients with stage IIIC EC treated with postoperative RT and ChT (paclitaxel and carboplatin). Patients were either treated with 6 cycles of ChT followed by RT (sequential arm; 96 patients) or with 3 cycles of ChT, RT, and an additional 3 cycles of ChT (sandwich arm; 83 patients). Prognostic factors affecting overall survival (OS) and progression-free survival (PFS) were analyzed.ResultsThe 5-year OS and PFS rates were 64% and 59%, respectively, with a median follow-up of 41 months (range, 5–167 months). The 5-year OS rates were significantly higher in the sandwich than sequential arms (74% vs. 56%; p=0.03) and the difference for 5-year PFS rates was nearly significant (65% vs. 54%; p=0.05). In univariate analysis, treatment strategy, age, International Federation of Gynecology and Obstetrics (FIGO) stage, pathology, rate of myometrial invasion, and grade were prognostic factors for OS and PFS. In multivariate analysis, non-endometrioid histology, advanced FIGO stage, and adjuvant sequential ChT and RT were negative predictors for OS, whereas only non-endometrioid histology was a prognostic factor for PFS.ConclusionPostoperative adjuvant ChT and RT for stage IIIC EC patients, either given sequentially or sandwiched, offers excellent clinical efficacy and acceptably low toxicity. Our data support the superiority of the sandwich regimen compared to the sequential strategy in stage IIIC EC patients for OS.

Postoperative Radiation Therapy (PORT) Is Safe and Effective in pIII-N2 Non-Small-Cell Lung Cancer (NSCLC) Receiving Pneumonectomy

For patients with pIII-N2 NSCLC who received pneumonectomy followed by adjuvant chemotherapy, there are few evidence on the use of PORT and its role remains controversial. This study is to evaluate the safety and efficacy of PORT for such population. Between Jan. 2004 and Dec. 2015, patients with stage pIII-N2 NSCLC who had undergone pneumonectomy followed by adjuvant chemotherapy with or without PORT in our institution were retrospectively reviewed. Platinum-based doublet chemotherapy of 4 cycles was used. Radiotherapy was performed by 3D-CRT/ IMRT to the total dose of 50-60 Gy. The effect of PORT on survival was evaluated by Kaplan-Meier method and log-rank test. Pearson chi-Square test was used to compare categorical variables between groups. Student-t test was used for normal distribution variables, and Mann-Whitney U test was used for non-normal distribution variables. Statistically significant difference was set as p<0.05. Totally 119 patients with stage pIII-N2 NSCLC were included in this study. Among them, 32 patients received sequential adjuvant chemotherapy and PORT (PORT group), and 87 patients received adjuvant chemotherapy alone (Control group). Clinical and pathological characteristics of patients between the two groups were comparable (p>0.05), which included age, gender, KPS, tumor site, preoperative lung function and pathological type, et al. R1/R2 resection of PORT group was significantly higher than that of Control group (25% vs. 8%, p=0.031). Grade 2 or above radiation induced acute or chronic pneumonitis was 2/ 32. No severe radiation induced heart injury was observed. There was no radiation toxicity related death. Of all the 119 patients, the median follow-up time was 25 months and median overall survival (mOS) was 46months. The median disease free survival (mDFS) was 15 months. OS in PORT group was significantly better than control group (not reached vs. 34 months, p=0.003), and so as to DFS (19 months vs. 13 months, p=0.003). PORT could also significantly increase local recurrence free survival (LRFS, p=0.012) and distant metastasis free survival (DMFS, p=0.047). In patients with R0 resection (n=104), OS and LRFS in PORT group were significantly higher than those in Control group, and postoperative radiotherapy tended to increase DFS and DMFS with curves not crossing. For paitients with R1/R2 resection (n=15), OS in PORT group was also significantly higher than that in Control group (not reach vs. 24 months, p=0.021). Compared with chemotherapy alone, adding radiotherapy significantly reduced local regional failure rate (39.1% vs. 15.6%, p=0.016), and distant metastasis was still the main cause of failure. For patients with stage pIII-N2 NSCLC after pneumonectomy followed by adjuvant chemotherapy, PORT was safe and could improve OS, DFS, LRFS and DMFS. Further verification of our result is needed in the future study.

Colored body images reveal the perceived intensity and distribution of pain in women with breast cancer treated with adjuvant taxanes: a prospective multi-method study of pain experiences.

Background and aims Breast cancer is the most prevalent adult cancer worldwide. A broader use of screening for early detection and adjuvant systemic therapy with chemotherapy has resulted in improved survival rates. Taxane-containing chemotherapy is one of the cornerstones of the treatment. However, taxane-containing chemotherapy may result in acute chemotherapy-induced nociceptive and neuropathic pain. Since this pain may be an additional burden for the patient both during and after taxane chemotherapy, it is important to rapidly discover and treat it. There is yet no gold standard for assessing taxane-induced pain. In the clinic, applying multiple methods for collecting information on pain may better describe the patients' pain experiences. The aim was to document the pain during and after taxane through the contribution of different methods for collecting information on taxane-induced pain. Fifty-three women scheduled for adjuvant sequential chemotherapy at doses of ≥75 mg/m2 of docetaxel and epirubicin were enrolled in the study. Methods Prospective pain assessments were done on a visual analog scale (VAS) before and during each cycle of treatment for about 5 months, and using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire's (EORTC-QLQ-C30) two pain questions at baseline, 3 months, and 12 months. Participants scoring pain on the VAS >30 and undergoing an interview also colored their pain on a body image during treatment and at 12 months. Results Surprisingly widespread, intense pain was detected using a multi-method approach. The colored body image showed pain being perceived on 51% of the body surface area during treatment, and on 18% 12 months after inclusion. In general, the pain started and peaked in intensity after the first cycle of taxane. After Cycle 3, most women reported an increase in pain on the VAS. Some women continued to report some pain even during the epirubicin cycles. The VAS scores dropped after the last chemotherapy cycle, but not to the baseline level. At baseline, 3 months and 12 months after inclusion, the women who estimated VAS >30 reported higher levels of pain on the pain questions of the EORTC-QLQ-C30. Conclusions This study contributes information on how different pain assessment tools offer different information in the assessment of pain. The colored body image brings another dimension to pain diagnostics, providing additional information on the involved body areas and the pain intensities as experienced by the women. A multi-method approach to assessing pain offers many advantages. The timing of the assessment is important to properly assess pain. Implications Pain relief needs to be included in the chemotherapy treatment, with individual assessment and treatment of pain, in the same way as is done in chemotherapy-triggered nausea. There is a time window whereby the risk of pain development is at its highest within 24-48 h after receiving taxane chemotherapy. Proper attention to pain evaluation and treatment should be in focus during this time window.