Therapeutic Effect Of Neoadjuvant Chemotherapy Research Articles

P2.02-004 Real-time Monitoring of Circulating Tumor Cells to Evaluate Response of Neoadjuvant Chemotherapy in Locally Advanced NSCLC

Enumeration and karyotyping of circulating tumor cells (CTCs) in therapeutic cancer patients is of particular clinical significance. The aim of this study is to evaluate therapeutic effect of neoadjuvant chemotherapy (NAC) by means of real-time monitoring of CTCs in locally advanced non-small cell lung cancer (NSCLC). Real-time monitoring of CTCs in the course of 2 cycles of platinum-based NAC was conduct in 34 locally advanced NSCLC patients. The integrated subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) method was applied to detect and characterize CTCs in peripheral venous blood. Chest CT was used to evaluate therapeutic response with RECIST 1.1 as the evaluation criterion. Of the 34 patients enrolled, 13 acquired partial response (PR) and 21 were stable diseases (SD) after NAC. The numbers of CTCs were found decrease in 70% of PR patients and only 25% of SD patients. The changes of CTC count were significantly different between PR and SD group (p=0.009). The positive rate of CTCs with triploidy of chromosome 8 increased after 2 cycles platinum-based NAC, and the elevation was even more remarkable in SD group. The changes of CTC count after NAC were in accordance with CT responses. Triploidy of chromosome 8 CTC was correlated with primary resistance to platinum-based chemotherapy. Real-time monitoring of CTC count and karyotype may be of clinical value in rapid evaluation of therapeutic effect and monitoring occurrence of chemo-resistance.

Platelet-Lymphocyte Ratio as a Useful Predictor of the Therapeutic Effect of Neoadjuvant Chemotherapy in Breast Cancer.

BackgroundThe peripheral blood platelet–lymphocyte ratio (PLR) has been proposed as an indicator for evaluating systemic inflammatory responses in cancer-bearing patients. While some reports suggest a correlation between PLR and prognosis, few studies have examined the relationship between PLR and sensitivity to chemotherapy. We conducted a study on whether PLR could serve as a predictor of the therapeutic effects of neoadjuvant chemotherapy (NAC).MethodsPLR was evaluated in 177 breast cancer patients treated with the NAC 5-fluorouracil, epirubicin and cyclophosphamide, followed by weekly paclitaxel and subsequent curative surgery. The correlation between PLR and prognosis, and between PLR and the efficacy of NAC, were evaluated retrospectively.ResultsThe low PLR group had significantly more patients > 56 years old (p = 0.001) and postmenopausal women (p = 0.001) than the high PLR group. The low PLR group also had a higher pathologic complete response (pCR) rate (p = 0.019). On examining the correlation with prognosis, the low-PLR group was found to have significantly longer disease-free survival (p = 0.004) and overall survival (p = 0.032) than the high PLR group. Multivariate analysis also revealed that lymph node metastasis (p = 0.043, hazard ratio = 4.40) and a high PLR (p = 0.005, hazard ratio = 2.84) were independent, unfavorable prognostic factors.ConclusionsFor patients with breast cancer treated with NAC, a low PLR indicated high chemotherapy sensitivity, suggesting that PLR could serve as a predictive marker of the therapeutic effect of NAC.

Abstract P6-01-08: BRCAness and prognosis in triple-negative breast cancer patients treated with neoadjuvant chemotherapy

Abstract <Background> Microarrays have shown that triple-negative breast cancers (TNBCs) are a heterogeneous group of disorders that have differential responses to chemotherapy. On the other hand, BRCA genes play an important role in DNA damage repair. Gene mutations and methylation of BRCAs causes functional abnormalities, leading to defects in DNA repair capacity. This state is called "BRCAness." In this study, we addressed BRCAness, therapeutic effects, recurrence, and prognosis in patients with TNBCs who were treated with neoadjuvant chemotherapy. <Subjects and Methods> We enrolled 40 patients with TNBC who were treated with neoadjuvant chemotherapy (anthracyclines alone in 3 patients and anthracyclines plus taxanes in 37 patients) at our hospital between April 2006 and October 2012. BRCAness was determined by preoperative core needle biopsy (CNB) specimens and surgical specimens. Genes from those specimens were amplified by multiplex ligation-dependent probe amplification (MLPA), and the amplicons were scored after separation by electrophoresis. With a cutoff value of 0.5, values of 0.5 or more were determined as the BRCA1-like Type (BRCAness) and those of less than 0.5 as the Sporadic Type to analyze clinical effects, pathological complete response (pCR) rate, recurrence, and prognosis. <Results> With regard to therapeutic effects of neoadjuvant chemotherapy, pCR (ypT0/Tis/N0) was observed in 15 patients and non-pCR in 25 patients (pCR rate: 37.5%). Twelve patients had recurrence after surgery, and 8 of whom died of the original disease. (1) The BRCA1-like Type accounted for 22 patients while the Sporadic Type accounted for 18 patients in CNB specimens. No major differences were observed between the BRCA1-like Type and Sporadic Type with regards to the pCR rate (7/22 vs. 5/18). Those two types had equivalent results in recurrence rate and prognosis. (2) Among the 24 non-pCR patients whose BRCA status could be determined by surgical specimens, 9 were found to be of the BRCA1-like Type. Patients with a BRCA1-like tumor had more recurrences (7/9 vs. 5/15), and their relapse-free survival was also lower (p<0.05). No association with prognosis was found. Six patients whose BRCA status of CNB specimens was of the BRCA1-like Type and that of surgical specimens turned to be of the Sporadic Type were better in recurrence (p<0.01) and prognosis (p<0.05), compared with seven patients whose BRCA status of surgical specimens remained to be of the BRVA-1 like Type. <Discussion> Patients with TNBC who achieved a pCR by neoadjuvant chemotherapy had a better prognosis even if the type is BRCA1-like. In contrast, the recurrence rate was higher when residual tumor remained after neoadjuvant chemotherapy and when the BRCA status became BRCA1-like. New clinical trials assessing the true recurrence (TR) rate of BRCA are expected since neither platinum-containing drugs nor poly (ADP-ribose) polymerase (PARP) inhibitors are effective against tumors with nonfunctional BRCA genes. Citation Format: Hirokazu Tanino, Yoshimasa Kosaka, Norihiko Sengoku, Mina Waraya, Hiroshi Nishimiya, Hirozhi Katoh, Mariko Kikuchi, Naoko Minatani, Saeko Teraoka, Takumo Enomoto, Takeo Sato, Masahiko Masahiko. BRCAness and prognosis in triple-negative breast cancer patients treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-01-08.

Combination of survivin siRNA with neoadjuvant chemotherapy enhances apoptosis and reverses drug resistance in breast cancer MCF-7 cells

Chemotherapeutic resistance is a main problem in clinical breast cancer therapy. The purpose of our study is to investigate whether the combination of neoadjuvant chemotherapy and survivin siRNA treatment could enhance the therapeutic effect of neoadjuvant chemotherapy using paclitaxel or epirubicin. The molecular cloning technique was applied to construct the expression vector of siRNA against survivin. Effectene Transfection Reagent was used to transfect plasmids to MCF-7 cells. Survivin expressions were detected by quantitative real-time PCR (qRT-PCR) and Western blot methods. The effect of paclitaxel or epirubicin, with or without the combination of survivin siRNA treatment, on drug susceptibility of MCF-7 cells was detected by CCK-8 assay. MCF-7 cell apoptosis was detected by Flow Cytometry. Survivin siRNA effectively inhibited the expression of Survivin RNA and protein levels (P < 0.05). Both paclitaxel and epirubicin can suppress the proliferation of MCF-7 cells and induce apoptosis to a certain degree respectively. The combination of survivin siRNA with the two chemotherapy drugs significantly enhanced both effects of the two chemotherapeutics respectively (P < 0.05). Survivin siRNA combined with the neoadjuvant chemotherapy can significantly enhance the sensitivity of MCF-7 cells to chemotherapeutics and cell apoptosis. This technology has important potential value in the therapeutic study of breast cancer.

Basic T1 Perfusion Magnetic Resonance Imaging Evaluation of the Therapeutic Effect of Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer

The objective of this study was to evaluate the dynamic changes of blood perfusion coinciding with tumor regression after neoadjuvant chemotherapy (NACT) in locally advanced cervical cancer (LACC). Thirty patients with LACC received conventional 3.0-T magnetic resonance imaging and perfusion-weighted imaging scans at 3 different times (before NACT, 2 weeks after the first NACT, and 2 weeks after the second NACT). Characteristics of time-intensity diagrams and patterns of blood perfusion maps according to the parameter of area under the curve (AUC) were observed. Eight perfusion parameters were compared among 3 time points at 2 different chemotherapy-sensitive groups by the software of Basic T1 Perfusion. The effective chemotherapy rate was 73.3% (22/30). The characteristic of time-intensity diagrams in cervical cancer was a rapid onset with plateau. There were 3 patterns of AUC perfusion maps. The common perfusion map was rich blood supply type in the effective chemotherapy group and peripheral blood supply type in the ineffective chemotherapy group. Four parameter values (relative enhancement, maximum enhancement, wash-in rate, and AUC) were significantly reduced 2 weeks after the second NACT than those before the therapy (P = 0.000; P = 0.009; P = 0.011; and P = 0.000) in the effective chemotherapy group, especially the value of relative enhancement 2 weeks after the first NACT, was obviously decreased compared to that before the therapy (P = 0.042). The value of time to peak 2 weeks after the second NACT was significantly longer than that before the therapy in the effective chemotherapy group (P = 0.001). There were no obvious changes of blood perfusion parameters among the 3 different times in the ineffective chemotherapy group. Tumor blood perfusion has obviously decreased after effective NACT in the treatment of LACC.

Therapeutic effect of neoadjuvant chemotherapy combined with docetaxel，oxaliplatin and capecitabine in the treatment of advanced gastric cancer

Objective: To investigate the therapeutic effect and adverse drug reactions(ADRs) of neoadjuvant chemotherapy combined with docetaxel,oxaliplatin and capecitabine(DOX regimen) in the treatment of advanced gastric cancer.Methods: One hundred and eighty-six patients with advanced gastric cancer in Department of Gastrointestinal Surgery,Changzheng Hospital,Second Military Medical University from 2008-06-01 to 2011-05-31 received neoadjuvant chemotherapy.Neoadjuvant chemotherapy regimen was as follows:75 mg/m2 docetaxel(iv gtt,on day 1),130 mg/m2 oxaliplatin(iv gtt,on day 2),1 000 mg/m2 capecitabine(bid,po,on days 1-14) with 3 weeks as one treatment course,totalling 2-3 courses.And the patients received surgery,2-3 weeks after termination of chemotherapy.Results: Total response rate was 67.8%,complete response rate was 3.8%(7 patients),partial response rate was 64.0%(119 patients).Total resection rate was 81.5%,R0 resection rate was 80.4%.Main ADRs were myelosuppression,nausea and vomiting.Conclusion: Overall curative resection rate was increased in patients with advanced gastric cancer,after neoadjuvant chemotherapy with docetaxel,oxaliplatin and capecitabine.The ADRs rate of neoadjuvant chemotherapy was within acceptable range.

DJ-1 as a predictor of pathologic complete remission of neoadjuvant chemotherapy with breast cancer patients.

10544 Background: DJ-1 is a multifunctional protein which is encoded by the causative gene of familial Parkinson disease (i.e., PARK7), and is associated with carcinogenesis. DJ-1 is also a candidate marker for the presence of breast cancer cells, in which it is secreted in nipple fluid and serum. We previously reported that a DJ-1 expression pattern that is low at the protein level and high at the mRNA level is associated with DJ-1 secretion. This secretory expression pattern correlated with a negative hormone receptor status and with unfavorable clinical outcome in breast cancer patients. However, the association of the DJ-1 secretion pattern with therapeutic effect has yet to be determined. Methods: A total of 299 patients received neoadjuvant chemotherapy and surgery from 2002 to 2010 at our institution. We performed immunohistochemistry and in-situ hybridization of DJ-1 in both the needle biopsy and operative specimens of 147 cases with a follow-up time of 3.1 years. The average degree of staining intensity was evaluated semi-quantitatively using an image analyzer. Univariate and multivariate analyses were used to evaluate the predictive value of the therapeutic effect of neoadjuvant chemotherapy. Results: A low expression of DJ-1 protein was detected in the needle biopsy and operative specimens of 89 of the 147 cases, regardless of a high or maintained mRNA level. The tumor response was evaluated as pathological complete remission (pCR) in 39 cases and as non-pCR in the remaining 108 cases. A low expression of DJ-1 protein, which was detected in 34 (87.2%) pCR cases, was a significant predictor on univariate analysis (P &lt;0.001). On multivariate analysis, a low expression of DJ-1 was shown to be a significant independent predictor similar to established predictors such as estrogen receptor status and human epidermal growth factor receptor 2 score. Conclusions: A low expression of DJ-1 protein can serve as a novel and important predictor of a neoadjuvant chemotherapeutic effect, as well as a promising indicator for serologic diagnosis in breast cancer patients.

P3-14-06: Combined Use of 18F-FDG PET/CT and MRI To Monitor Breast Cancer Response during Neoadjuvant Chemotherapy.

Abstract Background and aim: Contrast-enhanced breast magnetic resonance imaging (MRI) is commonly used for the evaluation of the therapeutic effect of neoadjuvant chemotherapy (NAC). A recent study demonstrated the relevance of breast cancer subtype with regard to the accuracy of MRI to predict response during NAC. The role of 18F-fluorodeoxyglucose (FDG) positron emission tomography (FDG PET/CT) is under investigation, and varying results have been reported. MRI and 18F-FDG PET/CT, visualize different functional characteristics of the tumor (perfusion and glucose metabolism), but it is unclear if they complement one another to monitor response to NAC, and whether breast cancer subtype plays an independent role. Method and material: The study group consisted of 65 women with stage II or III breast cancer and measurable FDG tumor uptake, who were treated with NAC and participated in an ongoing MRI/FDG PET/CT study. MRI and FDG PET/CT scans were acquired prior to and during treatment, using prone patient positioning. Written informed consent was obtained. Prior to the start of NAC a biopsy was taken and tumors were divided into three subtypes, using immunohistochemistry: human epidermal growth factor receptor 2 (HER2) amplified (HER2+) (N=18), estrogen receptor positive/HER2 non-amplified (ER+/HER2−) (N=29), and triple negative (TN) tumors (N=18). MRI interpretation included lesion morphology at baseline, changes in morphology, tumor size, and contrast uptake kinetics (initial and late enhancement). At FDG PET/CT the maximum standardized uptake value (SUVmax) at baseline and during treatment was obtained. Tumor response at pathology was stratified to “incomplete response” (substantial presence of vital invasive tumor cells) and “favourable response” (complete absence of invasive residual tumor or only a small number of scattered tumor cells). Appropriate statistical analyses including T-tests, multivariate logistic regression and receiver operating characteristic (ROC) curves were employed to indentify factors associated with incomplete response at pathology. The following imaging and clinical features were candidates for forward feature selection in the multivariate analysis: lesion morphology, largest tumor diameter, pattern of reduction, absolute and relative change in largest tumor diameter at initial and at late enhancement during NAC, SUVmax at baseline; absolute and relative change in SUVmax during NAC; breast cancer subtype; chemotherapy regimen, and age. Results: At pathology after NAC, 32 tumors (49 %) showed favourable response and 33 (51 %) had residual disease. At multivariate analysis, breast cancer subtype, relative change in the diameter of late enhancement on MRI and relative change in SUVmax on FDG PET/CT were independent markers of tumor response at final pathology. The area under the ROC curve increased from 0.86 for MRI alone to 0.94 (p&amp;lt;0.01) in combination with FDG PET/CT and breast cancer subtype, yielding 84% sensitivity at 95 % specificity. Conclusion: MRI and FDG PET/CT show complementary potential to predict response during NAC, in addition to breast cancer subtype. Ackowledgement: This study was supported by the Center for Translational Molecular Medicine, project Breast CARE (grant ***03O-104). Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-06.

Evaluation methods for the efficacy of neoadjuvant chemotherapy for breast cancer

With the widespread clinical application of neoadjuvant chemotherapy, it has become an essential part of combination therapy for patients with breast cancer. However, a rapid, accurate, and effective approach for assessing the therapeutic efficacy of neoadjuvant chemotherapy is unavailable. Routine physical examinations cannot provide effective clinical evaluation. Although imaging techniques play an important role in evaluating the therapeutic effect of neoadjuvant chemotherapy, this is limited because it only detects morphologic changes. Blood oxygen detection for breast diseases is an emerging diagnostic technique that has distinctive merit in assessing the efficacy of chemotherapy. Biologic markers are becoming more important in assessing the effect of neoadjuvant chemotherapy for patients with breast cancer. This review summarizes the principles and the current applied practice of these approaches to evaluate the effect of neoadjuvant chemotherapy for patients with breast cancer.

CT findings of breast cancer with clinically complete response following neoadjuvant chemotherapy - histological correlation

In breast cancer patients, several regimens of neoadjuvant chemotherapy have been developed in order to achieve prognostic advantages for individual patients. Though some percentages of breast cancer patients show clinically complete response to neoadjuvant chemotherapy, the histopathological specimens of these patients demonstrate a considerably high frequency of the existence of residual disease. In this study, we aimed to evaluate the therapeutic effect of neoadjuvant chemotherapy for breast cancer patients showing clinically complete response (cCR) to neoadjuvant chemotherapy, using thin-section (5 mm) helical CT (prone position) with bolus injection of contrast agent. Between April 1994 and March 2002, 9 patients with breast cancer showing cCR to the neoadjuvant chemotherapy, who had undergone thin-section CT study both before and following neoadjuvant chemotherapy, enrolled in the study. The mean age of the patients was 46.2 years and all of them were female. The clinical stages were, 8 patients in stage II, and one in stage IIIA. In the CT evaluation, residual disease was visualized in 5 out of the 9 patients. Histopathological examination disclosed the existence of residual cancers in 6 out of the 9 patients, but only non-invasive cancer was revealed in 1 out of the 6. As patients having residual disease composed only of non-invasive cancer are classified into the pathologically complete response group according to the WHO classification, 4 out of these 9 patients showing clinically complete response to the neoadjuvant chemotherapy were classified into pCR (pathologically complete response) group, and another 5 were classified into the pPR (pathologically partial response) group. As a result, the diagnostic accuracy of the second CT study performed after neoadjuvant chemotherapy was evaluated as 77.8%, with a sensitivity of 80.0%, a specificity of 75.0%, a positive predictive value (PPV) of 80.0%, and a negative predictive value (NPV) of 75.0%. Therefore, for precise evaluation of the neoadjuvant chemotherapeutic effect for breast cancer, thin-section CT studies are considered to be essential.

Thin-section CT evaluation and pathologic correlation of therapeutic effect of neoadjuvant chemotherapy for axillary lymph nodes of clinically node-positive breast cancer patients

In breast cancer patients, the number of surgically resected metastatic axillary lymph nodes has been considered to correlate closely with patient prognosis. Therefore, if metastatic lymph nodes could be controlled by neoadjuvant chemotherapy pre-operatively, we would be able to select a more appropriate regimen of post-operative chemotherapy for the individual patient and expect prognostic advantages of each patient with node-positive breast cancer. In this study, we aimed to evaluate the therapeutic effect of neoadjuvant chemotherapy for metastatic lymph nodes of node-positive breast cancer patients, using thin-section (5 mm) helical CT (prone-position) with bolus injection of contrast agent. Between April 1994 and March 2002, 49 patients with node-positive breast cancer who had undergone thin-section CT study both before and following neoadjuvant chemotherapy enrolled in the study. The mean age of the patients was 48.9 years and all were female. Concerning metastatic lymph nodes status, 45 patients were classified as N1, 2 patients as N2, and another 2 as N3. In the evaluation, if at least one lymph node of >5 mm in the short diameter was detected on the CT study, the case was classified as node-positive. For lymph nodes of >1 cm in short diameter, fine-needle aspiration biopsy guided by ultrasonography was performed in order to obtain pathological confirmation of the existence of cancer metastasis. The diagnostic results of the CT study were compared with the pathologic findings of the resected specimen operatively. The neoadjuvant chemotherapy consisted of 3 to 4 times of CAF chemotherapy and an anti-estrogen agent, and intra-arterial infusion chemotherapy was also performed in patients with lymph node status of N2 or N3. The axillary status of 15 (30.6%) out of the 49 patients was evaluated as N0 after neoadjuvant chemotherapy, and 14 out of the 15 patients were confirmed as node-negative based on the pathological results. Therefore, the diagnostic accuracy of the second CT study performed following the neoadjuvant chemotherapy was 85.7%, with a sensitivity of 96.6%, a specificity of 70.0%, a positive predictive value of 82.4%, and a negative predictive value of 93.3%. The results described above demonstrate that such a sophisticated and precise CT study performed following neoadjuvant chemotherapy and evaluating the therapeutic effect on metastatic lymph nodes following the neoadjuvant chemotherapy can help to determine an appropriate regimen of post-operative chemotherapy and be of prognostic advantage in patients with node-positive breast cancer.

Evaluation of neoadjuvant chemotherapeutic response of breast cancer using dynamic MRI with high temporal resolution.

The aim of this study was to evaluate changes in both size and contrast enhancement of breast tumors during neoadjuvant chemotherapy, using dynamic MRI with high temporal resolution. Patients with advanced breast cancer (n=21) underwent a 1.5-T MRI scan prior to and following neoadjuvant chemotherapy with four cycles. Dynamic contrast enhancement was measured using a fast turbo-FLASH sequence and quantified using a two-compartment model with the parameters k(ep) and amplitude. Image analysis was done on images overlayed with a color map of parameters. The correlation between tumor diameter measured by histopathology and MRI was 0.7 (p<0.003). A reduction of tumor size after chemotherapy of more than 25% was associated with a decrease of both analyzed contrast enhancement parameters (k(ep): p<0.002; amplitude: p<0.006), where k(ep) began to drop already after the first cycle of chemotherapy (p<0.008). A clear reduction of tumor size was only noted after the third cycle (p<0.008). In patients without tumor regression there was also a trend towards an early reduction of contrast enhancement. We assume that MRI with high temporal resolution and color mapping is a novel tool to assess therapeutic effects of neoadjuvant chemotherapy in breast tumors, which deserves further prospective evaluation.

Chemotherapy administered using two-route infusion of cisplatin and sodium thiosulfate and intravenous infusion of vinblastine and peplomycin in patients with oral cancer

The therapeutic effects of neo-adjuvant chemotherapy administered by two-route infusion of cisplatin and its antidote, sodium thiosulfate, and intravenous infusion of vinblastine and peplomycin were studied in 22 patients with previously untreated squamous cell carcinoma of the oral cavity or maxillary sinus. The overall response rate to chemotherapy was 90.9%, with a complete response in 12 patients (54.5%), a partial response in 8 patients (36.4%), and no change in 12 patients (9.1%). Histologic assessment showed a grade V response in 7 patients (31.8%), grade IV in 3 patients (13.6%), grade III in 5 patients (22.7%), grade II in 4 patients (18.2%), and grade I in 3 patients (13.6%). The cumulative 5-year survival rate, including 3 patients who died of another disease, was 72.2%. Leukocytopenia, an important side effect apparently induced by vinblastine, was seen, but no life-threatening complications occurred. Renal toxicity by cisplatin was minimal because of the use of sodium thiosulfate and fosfomycin. These data indicate that this mode of chemotherapy may be more effective for treating head and neck cancer than ordinary chemotherapy, from clinical and histologic stand-points. The high complete-response rate is especially noteworthy. No serious side effects or reductions in treatment period occurred. The results are preliminary and additional studies using a larger patient population are needed.

Positron emission tomography with L‐methyl‐11 C‐methionine in the monitoring of therapy response in muscle‐invasive transitional cell carcinoma of the urinary bladder

To investigate whether positron emission tomography (PET) with L-methyl-11C-methionine as a tracer could be used for diagnostic purposes and for evaluation of therapy in patients with varying stages of urinary bladder cancer treated with chemotherapy. PET was employed in 44 separate examinations involving 29 patients (24 men and five women with a median age of 68 years [mean 66, range 47-78]) with localized or metastatic transitional cell carcinoma of the urinary bladder. In four patients PET examinations were performed prior to the commencement of chemotherapy, and after one course and after three courses. The diagnostic accuracy of PET was poor. The technique did not monitor the therapeutic effect of neoadjuvant chemotherapy, producing results that correlated with therapy outcome. PET identified those patients who responded less successfully to therapy. PET with L-methyl-11C-methionine demonstrates alterations in tumour metabolism long before visible changes appear on computed tomography or magnetic resonance imaging. Further work is required to develop more specific tracers.

Patent statistics as related to the industrial development trend in Sweden in the period 1925–1936—I

The therapeutic effects of neo-adjuvant chemotherapy administered by two-route infusion of cisplatin and its antidote, sodium thiosulfate, and intravenous infusion of vinblastine and peplomycin were studied in 22 patients with previously untreated squamous cell carcinoma of the oral cavity or maxillary sinus. The overall response rate to chemotherapy was 90.9%, with a complete response in 12 patients (54.5%), a partial response in 8 patients (36.4%), and no change in 12 patients (9.1%). Histologic assessment showed a grade V response in 7 patients (31.8%), grade IV in 3 patients (13.6%), grade III in 5 patients (22.7%), grade II in 4 patients (18.2%), and grade I in 3 patients (13.6%). The cumulative 5-year survival rate, including 3 patients who died of another disease, was 72.2%. Leukocytopenia, an important side effect apparently induced by vinblastine, was seen, but no life-threatening complications occurred. Renal toxicity by cisplatin was minimal because of the use of sodium thiosulfate and fosfomycin. These data indicate that this mode of chemotherapy may be more effective for treating head and neck cancer than ordinary chemotherapy, from clinical and histologic stand-points. The high complete-response rate is especially noteworthy. No serious side effects or reductions in treatment period occurred. The results are preliminary and additional studies using a larger patient population are needed.