Response to neoadjuvant chemotherapy combined with regional hyperthermia predicts long-term survival for adult patients with retroperitoneal and visceral high-risk soft tissue sarcomas.

PURPOSE: To determine the efficacy of neoadjuvant chemotherapy combined with regional hyperthermia (RHT) for local tumor control and overall survival (OS) in adult patients with retroperitoneal or visceral (RP/V) high-risk soft tissue sarcomas (HR-STS). PATIENTS AND METHODS: From 1991 to 1997, 58 patients with HR-STS at RP/V sites were prospectively treated with four cycles of etoposide, ifosfamide, and doxorubicin combined with RHT followed by surgery, adjuvant chemotherapy, and radiation. RESULTS: Objective response rate assessable in 40 patients was 13% (five partial responses). Including minor responses (n = 8), the radiographic response rate was 33%. The pathologic response rate assessable in 26 patients after surgical resection was 42%. Median OS was 31 months. At a median observation time of 74 months, 5-year probability of local failure-free survival (LFFS), distant metastasis-free survival, event-free survival, and OS were 25%, 51%, 20%, and 32%, respectively. Averaged minimum temperatures (T(min)) and time-averaged temperatures achieved in 50% (T(50)) and 90% (T(90)) of all measured tumor sites differed significantly between responders and nonresponders (T(min), 39.3 degrees C v 38.0 degrees C; P =.002; T(50), 40.9 degrees C v 40.3 degrees C; P =.038; T(90), 40.1 degrees C v 39.3 degrees C; P =.017). At 5-year follow-up, probability of LFFS (59% v 0%; P <.001) and OS (60% v 10%; P <.001) was significantly in favor of patients responding to neoadjuvant thermochemotherapy. CONCLUSION: Response to neoadjuvant chemotherapy combined with RHT is predictive for an improved local tumor control resulting in a long-term survival benefit for patients with HR-STS at unfavorable RP/V sites; however, the impact of RHT has to be defined in a randomized phase III trial.     

Treatment of primary, recurrent or inadequately resected high-risk soft-tissue sarcomas (STS) of adults: results of a phase II pilot study (RHT-95) of neoadjuvant chemotherapy combined with regional hyperthermia

The efficacy of thermochemotherapy in adult patients with primary, recurrent or inadequately resected non-metastatic high-risk soft-tissue sarcomas (STS) was assessed. 54 patients were prospectively treated with four cycles of etoposide, ifosfamide and doxorubicin (EIA) combined with regional hyperthermia (RHT) followed by surgery, another four cycles of EIA without RHT and external beam radiation. The objective response rate was 16% and at a median follow-up time of 57 months, the 4-year estimated rates of local failure-free survival (LFFS), distant metastasis-free survival (DMFS), event-free survival (EFS) and overall survival (OS) were 59% (95% confidence interval (CI) 45-73%), 59% (95% CI 44-73%), 26% (95% CI 14-38%) and 40% (95% CI 27-53%), respectively. OS was in favour of patients responding to neoadjuvant treatment (P=0.073). In comparison to a preceding phase II study including pre- and postsurgical thermochemotherapy (RHT-91), at a 4-year follow-up the RHT-95 study cohort showed an inferior LFFS rate (P=0.027), but this did not affect DMFS (P=0.558) or OS (P=0.126). Hence, postsurgical thermochemotherapy seems critical for local tumour control without affecting survival.     

Long-term local control and survival after preoperative radiochemotherapy in combination with deep regional hyperthermia in locally advanced rectal cancer

Purpose: The aim of this study was to evaluate the impact of deep regional hyperthermia on long-term local control and survival in locally advanced non-metastatic rectal cancer. Methods: In total 103 patients with locally advanced non-metastatic rectal cancer were treated preoperatively with either neoadjuvant radiochemotherapy alone (n?=?43) or the same treatment with additional deep regional hyperthermia (n?=?60). The two groups were compared with respect to local control, overall survival (OS), disease-free survival (DFS), and distant metastases-free survival (DMFS). Results: Patients receiving additional hyperthermia had excellent long-term local control with a 5-year Kaplan-Meier estimate of 98% compared with 87% in the radiochemotherapy only group (p?=?0.09). Five-year rates for OS (88% versus 76%, p?=?0.08), DFS (77% versus 73%, p?=?n.s.) and DMFS (75% versus 77%, p?=?n.s.) were not statistically different between the two groups. Conclusion: Radiochemotherapy combined with hyperthermia results in excellent long-term local control.     

Radiologic and pathologic response to neoadjuvant chemotherapy predicts survival in patients undergoing the liver-first approach for synchronous colorectal liver metastases

Purpose

To investigate the short- and long-term outcomes of liver first approach (LFA) in patients with synchronous colorectal liver metastases (CRLM), evaluating the predictive factors of survival.

A phase I/II study of neoadjuvant liposomal doxorubicin,paclitaxel, and hyperthermia in locally advanced breast cancer

Purpose: The prognosis for locally advanced breast cancer (LABC) patients continues to be poor, with an estimated five-year survival of only 50–60%. Preclinical data demonstrates enhanced therapeutic efficacy with liposomal encapsulation of doxorubicin combined with hyperthermia (HT). Therefore this phase I/II study was designed to evaluate the safety and efficacy of a novel neoadjuvant combination treatment of paclitaxel, liposomal doxorubicin, and hyperthermia.

Materials and methods: Eligible patients received four cycles of neoadjuvant liposomal doxorubicin (30–75 mg/m²), paclitaxel (100–175 mg/m²), and hyperthermia. They subsequently underwent either a modified radical mastectomy or lumpectomy with axillary node dissection followed by radiation therapy and then eight cycles of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy.

Results: Forty-seven patients with stage IIB-III LABC were enrolled and 43 patients were evaluable. Fourteen patients (33%) had inflammatory breast cancer. Combined (partial + complete) clinical response rate was 72% and combined pathological response rate was 60%. Four patients achieved a pathologically complete response. Sixteen patients were eligible for breast-conserving surgery. The cumulative equivalent minutes (CEM 43) at T90 (tenth percentile of temperature distribution) was significantly greater for those with a pathological response. Four-year disease-free survival was 63% (95% CI, 46%–76%) and the four-year overall survival was 75% (95% CI, 58–86%).

Conclusions: Neoadjuvant therapy using paclitaxel, liposomal doxorubicin and hyperthermia is a feasible and well tolerated treatment strategy in patients with LABC. The thermal dose parameter CEM 43 T90 was significantly correlated with attaining a pathological response.     

Comparison of radiological and pathohistological response to neoadjuvant chemotherapy combined with regional hyperthermia (RHT) and study of response dependence on the applied thermal parameters in patients with soft tissue sarcomas (STS)

Purpose: To compare the radiological criteria RECIST, WHO, and tumor volume for evaluation of tumor response in patients with soft tissue sarcomas (STS) showing either good or poor pathohistological response to neoadjuvant chemotherapy combined with regional hyperthermia, and to examine the dependence of the findings on the applied thermal dose.

Materials and methods:19 patients with pathohistological complete response (no vital tumor cells, group 1) and 27 with pathohistological no response (<25% necrosis, group 2) were selected from our previous clinical trials. The change in tumor size before and after therapy was determined. Intratumoral temperature (T₉₀) and thermal dose (CEM 43°C T₉₀) were calculated for 13 patients.

Results: In the first group, 6 partial response (PR) and 13 stable disease (SD) according to RECIST, 7 PR and 12 SD according to WHO, 7 PR and 12 SD according to volumetric criteria were evaluated. In the second group, the results were 10 PR and 17 SD (RECIST), 9 PR and 18 SD (WHO), 8 PR and 19 SD (volume). The concordance of these criteria was 73.7% in group 1 and 74% in group 2. PR and SD were equally distributed in both groups (p > 0.421). Thermal parameters were not different between the groups (p > 0.327).

Conclusions: SD or PR in radiological response assessment does not correlate with the pathohistological response after neoadjuvant thermochemotherapy. RECIST, WHO and volumetric criteria for response evaluation in STS are in substantial agreement. For irregularly shaped lesions, volumetric criteria seem to be more appropriate.     

Low drug resistance to both platinum and taxane chemotherapy on an in vitro drug resistance assay predicts improved survival in patients with advanced epithelial ovarian,fallopian and peritoneal cancer

The objective of this study was to evaluate the role of an in vitro drug resistance assay to platinum and taxane in the management of advanced epithelial ovarian, fallopian and primary peritoneal cancer. All patients with FIGO Stage IIIc and IV who received postoperative chemotherapy with platinum and taxane for more than 4 courses after the initial cytoreductive surgery between 1995 and 2008 were evaluated. Patients who received neoadjuvant chemotherapy were not included. An in vitro drug resistance assay (EDR Assay, Oncotech, Tustin, CA) was used to determine drug resistance for each patient's tumor tissue. Level of drug resistance was described as extreme (EDR), intermediate (IDR), or low (LDR). Response to chemotherapy and survival were correlated to the EDR Assay. Of the 335 patients who underwent primary cytoreductive surgery, 173 cases met the criteria for statistical evaluation. The 58 patients (33.5%) whose tumors had LDR to both platinum and taxane had statistically improved progression‐free survival and overall survival (OS) compared with the 115 patients (66.5%) who demonstrated IDR or EDR to platinum and/or taxane (5‐year OS rates, 41.1% vs. 30.9%, p = 0.014). The 5‐year OS rates for the 28 (16.2%) cases that had optimal cytoreduction with LDR to both platinum and taxane was significantly improved over the 62 (35.8%) cases that were suboptimally cytoreduced with IDR or EDR to platinum and/or taxane (54.1% vs. 20.4%, respectively, p < 0.001). In conclusion, LDR to both platinum and taxane chemotherapy, as determined by an in vitro drug resistance assay, independently predicts improved survival in patients with advanced epithelial ovarian, fallopian and peritoneal cancer, especially in those patients who undergo optimal primary cytoreduction. © 2009 UICC     

Prevalence and clinical impact of TP53 germline mutations in Chinese women with breast cancer

The prevalence and clinical relevance of TP53 germline mutations in a large unselected breast cancer series are largely unknown. Here, we determined TP53 germline mutations in a large cohort of 10,053 unselected breast cancer patients through multigene panel-based next-generation and/or Sanger sequencing assays. We found that 0.5% of patients (50 cases) carried a pathogenic TP53 germline mutation in this large series of 10,053 unselected breast cancer patients, and the prevalence of TP53 germline mutation was 3.8% in very early onset breast cancer (age ≤30 years) in this large cohort. TP53 mutation carriers were significantly more likely to have early onset cancer (p < 0.001) and bilateral breast cancer (p = 0.03), they and were significantly more likely to respond to carboplatin-based neoadjuvant chemotherapy compared to anthracycline- or taxane-based regimen in terms of pathologic complete response (50% vs. 0%, p = 0.006). At the median follow-up of 54 months, TP53 mutation was an independent unfavorable factor for recurrence-free survival (RFS), distant recurrence-free survival (DRFS), and overall survival (OS) (RFS, adjusted hazard ratio [HR]: 2.24, 95% confidence interval [CI]: 1.15–4.33, p = 0.02; DRFS, adjusted HR: 2.73, 95% CI: 1.41–5.30, p = 0.003; OS, adjusted HR: 4.60, 95% CI: 2.26–9.41, p < 0.001) in multivariate analyses. Our study suggested that TP53 germline mutations occur more frequently in very early onset unselected breast cancer patients; and TP53 germline mutation carriers have a very poor survival and may benefit from carboplatin-based neoadjuvant chemotherapy in unselected breast cancer patients.     

Prognostic factors associated with survival in a large cohort of gastric cancer patients resected over a decade at a single Italian center: the Cremona experience

Background

Incidence of gastric cancer (GC) shows different distribution in Italy, with higher incidence in the north and center. We retrospectively analyzed the clinical data of patients resected at the Hospital of Cremona between January 2007 and December 2016. Available clinical variables were linked with survival to identify possible prognostic factors.

Materials and methods

Variables analyzed were age, sex, type of surgery, site, histology, invasion, nodal status, resection margins, grade, HER2 status, Helicobacter pylori infection (neo)adjuvant chemotherapy, adjuvant chemoradiotherapy, neutrophil-to-lymphocyte ratio, number of nodes removed and type of lymphadenectomy. Overall survival (OS) was estimated by the Kaplan–Meier method and differences between groups by the log-rank test. Data on OS were analyzed by Cox regression and the final model was obtained using the step-wise method.

Results

379 patients were considered, out of which 195 were operated from 2007 to 2011 and 184 from 2012 to 2016. Median follow-up was 25.5 months, median OS 31.3 months and time to recurrence 23.2 months. D2 resection rate increased from 36% (period 2007–2011) to 74% in 2012–2016 (p?=?0.01) with a higher mean number of nodes collected (20.98 for 2007–2011 and 23.53 for 2012–2016, p?=?0.040). Only 37% of patients received a postoperative treatment. At multivariate analysis, variables associated with OS were age (p?=?0.002), stage (p?<?0.001), resection margins status (p?<?0.001), adjuvant chemotherapy (p?<?0.010) and tumor location (cardia vs non-cardia) (p?=?0.029).

Conclusions

Our analysis shows that completeness of resection and lower stage are strong predictors of long-term survival in GC, providing the rationale for adjuvant and neoadjuvant approaches (chemotherapy, radiotherapy or combined). Cardial GC has worse prognosis compared to distal cancers.

Trial registration number

Service evaluation number 256, protocol 16821/17, date 05 June 2017.

     

Intracavity hyperthermia in nasopharyngeal cancer: A phase III clinical study

Purpose: To compare the local tumour control, survival, and acute mucous toxicity of nasopharyngeal cancer (NPC) patients treated with conventional radiotherapy (RT) combined with intracavity hyperthermia versus conventional RT alone.

Methods and materials: Previously untreated NPC patients were assigned randomly into the conventional RT group and the hyperthermia group. In addition to curative RT, hyperthermia group patients received intracavity hyperthermia before or after RT; T90 was 42.5°–43°C for 50 min twice a week for 7 weeks.

Results: From August 2001 to July 2006, 180 eligible patients with NPC were enrolled in this study. The complete response (CR) rate in the two arms (RT plus hyperthermia versus conventional RT) was 95.6% and 81.1%, respectively (p = 0.003, χ² test). CR rates for T2 and T3 patients in the hyperthermia group were 97.1% and 96.9%, respectively, while in the conventional RT group they were 79.5% and 76.7%, respectively. The difference between the two groups was statistically significant (p = 0.03 and p = 0.024, respectively). The 5-year local control rate was 91.1% and 78.9% for the two arms, respectively (p = 0.022). Oral mucous toxicity in both arms was comparable. The 5-year PFS and 5-year OS rate for the hyperthermia arm vs. the conventional arm were 72.7% versus 63.1% (p = 0.039) and 78.2% versus 70.3% (p = 0.14), respectively.

Conclusions: Conventional RT treatment followed by intracavity hyperthermia was well tolerated by the NPC patients. The addition of hyperthermia improved the local tumour control, and our results indicated a positive impact on PFS of NPC patients.     

The clinical benefit of hyperthermia in pancreatic cancer: a systematic review

Objective: In pancreatic cancer, which is therapy resistant due to its hypoxic microenvironment, hyperthermia may enhance the effect of radio(chemo)therapy. The aim of this systematic review is to investigate the validity of the hypothesis that hyperthermia added to radiotherapy and/or chemotherapy improves treatment outcome for pancreatic cancer patients.

Methods and materials: We searched MEDLINE and Embase, supplemented by handsearching, for clinical studies involving hyperthermia in pancreatic cancer patients. The quality of studies was evaluated using the Oxford Centre for Evidence-Based Medicine levels of evidence. Primary outcome was treatment efficacy; we calculated overall response rate and the weighted estimate of the population median overall survival (m_p) and compared these between hyperthermia and control cohorts.

Results: Overall, 14 studies were included, with 395 patients with locally advanced and/or metastatic pancreatic cancer of whom 248 received hyperthermia. Patients were treated with regional (n?=?189), intraoperative (n?=?39) or whole-body hyperthermia (n?=?20), combined with chemotherapy, radiotherapy or both. Quality of the studies was low, with level of evidence 3 (five studies) and 4. The six studies including a control group showed a longer m_p in the hyperthermia groups than in the control groups (11.7 vs. 5.6?months). Overall response rate, reported in three studies with a control group, was also better for the hyperthermia groups (43.9% vs. 35.3%).

Conclusions: Hyperthermia, when added to chemotherapy and/or radiotherapy, may positively affect treatment outcome for patients with pancreatic cancer. However, the quality of the reviewed studies was limited and future randomised controlled trials are needed to establish efficacy.     

Effects of the number of neoadjuvant therapy cycles on clinical outcomes,safety, and survival in patients with metastatic colorectal cancer undergoing metastasectomy

The controversial outcomes in patients with metastatic colorectal cancer (mCRC) highlight the need for developing effective systemic neoadjuvant treatment strategies to improve clinical results. The optimal treatment cycles in patients with mCRC for metastasectomy remain undefined. This retrospective study compared the efficacy, safety, and survival of cycles of neoadjuvant chemotherapy/targeted therapy for such patients. Sixty-four patients with mCRC who received neoadjuvant chemotherapy/targeted therapy following metastasectomy were enrolled between January 2018 and April 2022. Twenty-eight patients received 6 cycles of chemotherapy/targeted therapy, whereas 36 patients received ≥7 cycles (median, 13; range, 7–20). Clinical outcomes, including response, progression-free survival (PFS), overall survival (OS), and adverse events, were compared between these two groups. Of the 64 patients, 47 (73.4%) were included in the response group, and 17 (26.6%) were included in the nonresponse group. The analysis revealed chemotherapy/targeted therapy cycle and pretreatment serum carcinoembryonic antigen (CEA) level as independent predictors of the response as well as overall survival and chemotherapy/targeted therapy cycle as an independent predictor of progression (all p < 0.05). Furthermore, our results revealed shorter operation time, lower estimated operative blood loss, higher response rate, lower progression rate, and higher survival rate in ≥7 cycles of chemotherapy/targeted therapy group (all p < 0.05), but no statistical differences in adverse events were observed between the two groups (all p > 0.05). The median OS and PFS were 48 months (95% CI, 40.855–55.145) and 28 months (95% CI, 18.952–37.48) in the ≥7-cycle group and 24 months (95% CI, 22.038–25.962) and 13 months (95% CI, 11.674–14.326) in the 6-cycle group, respectively (both p < 0.001). The oncological outcomes in the ≥7-cycle group were significantly better than those in the 6-cycle group, without significant increases in adverse events. However, prospective randomized trials are mandatory to confirm the potential advantages of cycle numbers of neoadjuvant chemotherapy/targeted therapy.     

Chirurgische Therapie von Weichteilsarkomen der Extremitäten

Background

Surgery with curative intention in multimodal treatment concepts for patients with soft tissue sarcomas is the most important prognostic factor. Clear resection margins (R0) are one of the most important prognostic factors especially in the prevention of local recurrence and probably also in the overall survival of the disease. If R0 resection seems to be possible or can only be realized with mutilating procedures, neoadjuvant therapy concepts must be considered.

Objective

The principles of surgical therapy in patients with soft tissue sarcomas including multimodal strategies are discussed.

Material and methods

A systematic literature review of original articles and review articles over the last 15 years was performed. No prospective, randomized studies on surgery of soft tissue sarcomas were identified. The publications are discussed and assessed.

Results

In recent decades it could be shown that a compartmental resection has no significant advantages over wide resection with respect to local recurrence rate and overall survival. In the literature the rate of local recurrence is cited as being between 10?% and 40?% and the 5-year overall survival for all patients is approximately 50?%. In wide resections the ideal safety margin is not clearly defined. An R0 resection is therefore the most important criterion. A safety margin of at least 1 cm in all directions, as has been recommended for many years, can no longer be justified, the only exception being for liposarcoma (G1), the atypical lipoma of the extremities. Systemic chemotherapy (with or without hyperthermia) or radiotherapy can be beneficial and necessary in a multimodal neoadjuvant or adjuvant setting. With neoadjuvant radiotherapy a significantly increased rate of wound healing problems (>?30?%) in patients must be considered. Isolated hyperthermic limb perfusion (ILP) together with tumor necrosis factor alpha (TNF-alpha) and melphalan is an effective treatment option for patients with locally advanced soft tissue sarcomas of the extremities if an R0 resection could only be achieved by functional or anatomical amputations. Using this procedure allows resection of the soft tissue sarcoma and limb salvage in 81?% of patients. Reconstructive operative methods including flap surgery, vessel reconstruction and mesh grafts can be performed in approximately 20?% of patients.

Conclusions

A planned multidisciplinary concept from primary imaging, radiology, biopsy to histopathological investigation is necessary for defining the multimodal therapy and follow-up of patients with a soft tissue sarcoma. Surgery is still the key factor for local control and overall survival. The standard of care for soft tissue sarcomas of the extremities, with the exception of atypical lipoma, is a wide resection (R0). An ultraradical resection including vital structures for extending an already foreseeable free margin (R0) does not show any benefits. If a resection or re-resection cannot be performed in sano (i.e. R1), additional adjuvant or neoadjuvant radiotherapy should be included. The ILP procedure including TNF-alpha and melphalan is an effective treatment option in selected cases for patients with locally advanced soft tissue sarcomas of the extremities to avoid functional or anatomical amputations.     

Duration of letrozole treatment and outcomes in the placebo-controlled NCIC CTG MA.17 extended adjuvant therapy trial

SummaryPurpose MA.17 was a double-blind placebo-controlled trial involving 5187 postmenopausal women that established letrozole to be of value in reducing recurrence of breast cancer when given in the extended adjuvant therapy setting after about 5 years of tamoxifen. Analyses were conducted to examine the relationships between duration of treatment on MA.17 and outcomes.Methods The final MA.17 database that included all events up to the date of unblinding of the study was interrogated. A non-parametric kernel smoothing method was used to estimate the hazard rates for disease-free survival (DFS), distant DFS (DDFS) and overall survival (OS) at 6, 12, 24, 36 and 48 months of follow-up and the hazard ratios (HRs) of letrozole to placebo were determined. The trend in HRs over time was tested based on a Cox model with a time-dependent covariate.Results Considering all patients, HRs for events in DFS and DDFS progressively decreased over time, favoring letrozole, with the trend being significant (p<0.0001 and p=0.0013, respectively) whereas the trend for OS was not significant. Considering the 2360 patients with node-positive status, the HRs for DFS, DDFS and OS all decreased over time with tests for trend all showing significance (p=0.0004, 0.0005 and 0.038, respectively). Considering the 2568 patients with node-negative status, the HRs for DFS decreased over time with the test for trend being significant (p=0.027) whereas the HRs for DDFS and OS showed no significant change over time.Conclusion These analyses suggest that, at least out to about 48 months, longer duration of letrozole treatment is associated with greater benefit in the extended adjuvant therapy setting.     

Identification and analysis of <Emphasis Type="Italic">CHEK2</Emphasis> germline mutations in Chinese <Emphasis Type="Italic">BRCA1/2</Emphasis>-negative breast cancer patients

Purpose

The estrogen receptor (ER) is involved in control of progesterone receptor (PgR) expression and lack of PgR may be also a surrogate of altered growth factor signaling. The aim of this study was therefore to investigate PgR expression as predictive factor for response to neoadjuvant therapy and long-term outcome.

Methods

Five thousand and six hundred and thirteen patients with primary breast cancer and positive ER expression from ten German neoadjuvant trials of anthracycline and taxane-based chemotherapy were included. Pathologic complete response (pCR), disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and local recurrence-free survival (LRFS) were compared according to PgR expression.

Results

The lack of PgR expression (1172 patients) was associated with grade 3 (38.4 vs. 26.3%; p < 0.001), nodal involvement (>cN2) (6.8% vs. 4.7%; p = 0.004), and HER2 positivity (36.2 vs. 22.3%; p < 0.001). pCR rates of PgR-negative tumors were higher in the entire cohort (13.8 vs. 7.5%; p < 0.001) and in the HER2-negative subgroup (11.2 vs. 5.8%; p < 0.001). In multivariable logistic regression, PgR negativity was an independent predictive factor for pCR overall (OR 1.76; p < 0.001) and in the HER2-negative patients (OR 1.99; p < 0.001). Patients with PgR-negative disease had significantly worse outcome (p < 0.001, respectively). Multivariable Cox regression analysis revealed that PgR was an independent prognostic factor for DFS, OS, DDFS, and LRFS.

Conclusion

ER-positive/PgR-negative breast carcinomas are associated with higher response but also worse long-term outcome after neoadjuvant therapy. PgR negativity is an independent predictive factor for pCR after neoadjuvant chemotherapy in ER-positive HER2-negative breast cancer.

     

Short-term Intensive Neoadjuvant Chemotherapy Improving 10-year Survival for Patients with Stage Ⅱ and Operable Stage Ⅲ Breast Cancer

Objective To evaluate the 10-year curative effects of short-term intensive neoadjuvant chemotherapy for operable breast cancer. Methods A total of 510 patients with stagell and operable stagelll breast cancer were divided into group A (preoperative neoadjuvant chemotherapy 251 cases) and group B (postoperative adjuvant chemotherapy 259 cases). The patients in group A received short -term and intensive neoadjuvant chemotherapy for 4 weeks followed by modified radical mastectomy two weeks after the chemotherapy. The postoperative adjuvant chemotherapy began within two weeks after surgery. The same chemotherapeutic regimen was used for both groups. Results For stage III in group A the 5-year overall survival rate (OS) and disease-free survival rate (DFS) were 59.2% and 54.9% respectively which were higher than those in group B (28.3% and 20.8% respectively,P<0.05). The 10-year OS and DFS were 78.1% and 73.5% respectively for stage II in group A which were higher than those in group B (68.4% and 60.7%,P< 0.05). The 10-year OS and DFS were 42.3% and 40.4% respectively for stage III in group A which were higher than those in group B (20.4% and 18.4% respectively,P<0.05). Conclusion The results showed that intensive neoadjuvant chemotherapy can improve the 10-year survival for patients with stage II and operable stage III breast cancer.     

成人高风险性软组织肉瘤的多形性治疗

Objective： We enrolled retrospective data to determine the efficacy of combined chemotherapy and surgery for local tumour control and survival in patients with high-risk soft-tissue sarcomas. Methods： We collected data from 25 patients with high-risk soft-tissue sarcomas treated with four cycles of etoposide, ifosfamide and doxorubicin （EIA） followed by definitive surgery with or without postoperative radiotherapy and adjuvant chemotherapy. 21 patients received chemotherapy in a neoadjuvant/adjuvant clinical setting; eighteen of them completed adjuvant chemotherapy. Four patients received chemotherapy in an adjuvant setting only. Results： The objective response rate of neoadjuvant chemotherapy assessable in 21 patients was 43%. Including NED （n=7） and partial remissions （n=3）, the radiographic response rate was 47.6% with additional 42.9% stable diseases （n=9）. Surgery was performed in two patients before completing four neoadjuvant chemotherapy cycles because of disease progression. Median overall survival for all patients was 21.6＋ months. After completion of chemotherapy, in 62% of patients R0-resection could be performed. Conclusion： High proportion of R0-resections supports the idea of tumour down-staging after neoadjuvant treatment. Response to neoadjuvant chemotherapy is predictive for improved local tumour control resulting in long-term survival benefit.     

Long-term outcomes of neoadjuvant chemotherapy before chemoradiation for locally advanced pancreatic cancer

BACKGROUND:

Neoadjuvant chemotherapy before chemoradiation therapy (CRT) may improve outcomes for patients with locally advanced pancreatic cancer, but optimal management remains controversial, and prior reports have limited follow‐up.

METHODS:

Seventy consecutive patients with unresectable (n = 46) or borderline resectable (n = 24) locally advanced pancreatic cancer were treated with CRT from 2005 to 2009. Patients typically received 50.4 grays in 28 fractions (91%) with concurrent 5‐fluorouracil (84%) or capecitabine (14%). Forty patients received CRT alone, and 30 patients received neoadjuvant chemotherapy before CRT for a median of 4 months, typically gemcitabine (93%). All patients without progression after neoadjuvant chemotherapy were offered CRT.

RESULTS:

Median follow‐up was 14.2 months (range, 3‐57 months). Fifty‐three percent of patients in the CRT group versus 83% in the neoadjuvant chemotherapy before CRT group had unresectable tumors at diagnosis; after completion of CRT, 20% of patients in both groups underwent resection. Compared with CRT alone, the neoadjuvant chemotherapy before CRT group demonstrated improved median overall survival (OS; 18.7 vs 12.4 months; P = .02) and progression‐free survival (11.4 vs 6.7 months; P = .02). On multivariate analysis, receipt of neoadjuvant chemotherapy (adjusted hazard ratio [HR], 0.49; 95% CI, 0.28‐0.87; P = .02) and surgical resection (adjusted HR, 0.38; 95% CI, 0.17‐0.85; P = .02) were associated with increased OS.

CONCLUSIONS:

Gemcitabine‐based neoadjuvant chemotherapy confers a significant OS advantage by allowing the selection of patients who will derive greatest benefit from CRT. Median survival with this approach was similar to that seen with surgical resection. Cancer 2012;118: 3026–35. © 2011 American Cancer Society.     

Tumor-related leukocytosis is associated with poor radiation response and clinical outcome in uterine cervical cancer patients

BackgroundTo evaluate response to radiation and clinical outcome of uterine cervical cancer patients with tumor-related leukocytosis (TRL) at initial diagnosis and during definitive radiotherapy.Patients and methodsWe retrospectively analyzed 2456 patients with stage IA–IVA uterine cervical cancer who received definitive radiotherapy with (37.4%) or without (62.6%) platinum-based chemotherapy between 1986 and 2012. TRL was defined as two or more occurrences of leukocytosis over 9000/μl at the time of diagnosis and during the course of treatment. Locoregional failure-free survival (LFFS) and overall survival (OS) were compared between patients with or without TRL.ResultsThe median age of all patients was 55 years, and the median follow-up time was 65.1 months. TRL was observed in 398 patients (16%) at initial diagnosis; TRL (+) patients were younger and had larger tumors, advanced stage, and more frequent lymph node metastases (all P < 0.05). TRL (+) patients showed a significantly lower rate of complete remission than TRL (-) patients (89.9% versus 96.3%, respectively, P = 0.042). Ten-year LFFS and OS for all patients were 84% and 78%, respectively. LFFS and OS were significantly lower in TRL (+) patients than TRL (-) patients (10-year LFFS: 69% versus 87% respectively, P < 0.001; 10-year OS: 63% versus 81% respectively P < 0.001). After propensity score matching, LFFS and OS rates in TRL (+) patients remained significantly lower than for TRL (-) patients; this significant difference was also observed on multivariate analysis. Twenty-six percent of patients with locoregional failure (n = 345) were TRL (+) and had significantly poorer median OS (6 versus 12 months, P = 0.001).ConclusionThis study reveals the aggressive nature of cervical cancer with TRL and its poor response to radiation therapy. Given the unfavorable prognosis and higher probability of treatment failure, optimal diagnostic and therapeutic approaches and careful monitoring for early detection of recurrence should be considered for these patients.     

A comparison of the outcomes of neoadjuvant and adjuvant chemotherapy for clinical T2-T4aN0-N2M0 bladder cancer

BACKGROUND:

Despite evidence supporting perioperative chemotherapy, few randomized studies compare neoadjuvant and adjuvant chemotherapy for bladder cancer. Consequently, the standard of care regarding the timing of chemotherapy for locally advanced bladder cancer remains controversial. We compared patient outcomes following neoadjuvant or adjuvant systemic chemotherapy for cT2‐T4aN0‐N2M0 bladder cancer.

METHODS:

In a retrospective review of a single institutional database from 1988 through 2009, we identified patients receiving neoadjuvant or adjuvant multiagent platinum‐based systemic chemotherapy for locally advanced bladder cancer. Survival analysis was performed comparing disease‐specific survival (DSS) and overall survival (OS).

RESULTS:

A total of 146 patients received systemic perioperative chemotherapy (73 neoadjuvant, 73 adjuvant). Of these, 84% (122/146) received cisplatin‐based chemotherapy compared with carboplatin‐based chemotherapy (24/146, 16.4%). Most patients receiving cisplatin‐based chemotherapy were treated with methotrexate/vinblastine/adriamycin/cisplatin (79/122, 64.8%), whereas the remaining patients received gemcitabine/cisplatin (GC) (43/122, 35.2%). In multivariable analysis, there was no significant difference in DSS (P = .46) or OS (P = .76) between neoadjuvant or adjuvant chemotherapy groups. There was statistically significant improvement in DSS when patients received neoadjuvant GC rather than adjuvant GC (P = .049, hazard ratio, 10.6; 95% confidence interval, 1.01‐112.2).

CONCLUSION:

In this study, there was no statistically significant difference in OS and DSS between patients receiving neoadjuvant versus adjuvant systemic platinum‐based chemotherapy for locally advanced bladder cancer. In addition, there was no significant difference between neoadjuvant and adjuvant cisplatin‐ or carboplatin‐based chemotherapy. Chemotherapy sequence relative to surgery appeared less important than whether or not a patient actually received perioperative chemotherapy. Cancer 2011;. © 2011 American Cancer Society.