Adherence to treatment guidelines for primary sarcomas affects patient survival: a side study of the European CONnective TIssue CAncer NETwork (CONTICANET).

BACKGROUND: The impact of adherence to clinical practice guidelines (CPGs) for loco-regional treatment (i.e. surgery and radiotherapy) and chemotherapy on local disease control and survival in sarcoma patients was investigated in a European study conducted in an Italian region (Veneto). PATIENTS AND METHODS: The completeness of the adherence to the Italian CPGs for sarcomas treatment was assessed by comparing the patient's charts and the CPGs. Propensity score-adjusted multivariate survival analysis was used to assess the impact of CPGs adherence on patient clinical outcomes. RESULTS: A total of 151 patients were included. Adherence to CPGs for loco-regional therapy and chemotherapy was observed in 106 out of 147 (70.2%) and 129 out of 139 (85.4%) patients, respectively. Non-adherence to CPGs for loco-regional treatment was independently associated with AJCC stage III disease [odds ratio (OR) 1.77, P = 0.011] and tumor-positive excision margin (OR 3.55, P = 0.003). Patients not treated according to the CPGs were at a higher risk of local recurrence [hazard ratio (HR) 5.4, P < 0.001] and had a shorter sarcoma-specific survival (HR 4.05, P < 0.001), independently of tumor stage. CONCLUSIONS: Incomplete adherence to CPGs for loco-regional treatment of sarcomas was associated with worse prognosis in patients with non-metastatic tumors.

Intratumor morphologic and transcriptomic heterogeneity in V600EBRAF-mutated metastatic colorectal adenocarcinomas.

BACKGROUND: Intratumor heterogeneity (ITH) is described as the presence of various clones within one tumor, each with their own unique features in terms of morphology, inflammation, genetics or transcriptomics. Heterogeneity provides the fuel for drug resistance; therefore, an accurate assessment of tumor heterogeneity is essential for the development of effective therapies. The purpose of this study was to dissect morphologic and molecular ITH in colorectal adenocarcinoma. MATERIALS AND METHODS: A series of 120 V600EBRAF-mutated (V600EBRAFmt) consecutive metastatic colorectal adenocarcinomas was assessed for morphologic heterogeneity. The two heterogeneous components of each specimen underwent a histopathological, immunohistochemical and molecular characterization to evaluate: histologic variant, grading, tumor-infiltrating lymphocytes (TILs), mismatch repair proteins' expression, KRAS/BRAF/NRAS mutations, microsatellite instability (MSI) status and consensus molecular subtype (CMS). RESULTS: Thirty-one out of 120 (25.8%) V600EBRAFmt primary colorectal adenocarcinomas presented a heterogeneous morphology. Among these, eight cases had adequate material for molecular profiling. Five out of the eight (62.5%) cases resulted instable at MSI testing. The majority (62.5%) of the samples showed a CMS4 phenotype based on gene expression profiling. Heterogeneity in CMS classification was observed in four out of eight cases. One out of eight cases presented significant heterogeneity in the number of TILs between the two components of the tumor. CONCLUSIONS: Although the distribution of the immune infiltrate appears relatively conserved among heterogeneous areas of the same tumor, changes in gene expression profile and CMS occur in 50% of V600EBRAFmt adenocarcinoma cases in our small series and might contribute to variability in response to anticancer therapy and clinical outcomes. Assessment of morphological and molecular ITH is needed to improve colorectal cancer classification and to tailor anticancer treatments and should be included in the pathology report.

COVID-19 seroprevalence in military police force, Southern Brazil.

BACKGROUND: Limited data is available regarding the frequency of COVID-19 in populations that are highly exposed to SARS-CoV-2. In this cross-section study we evaluated COVID-19 seroprevalence in military police forces of 10 major cities in Rio Grande do Sul, South of Brazil. METHODS: Sampling was randomly performed in clusters, in respect to the number of professionals at service per city and military unit. Research subjects were evaluated on July 23, 2020 (first wave peak in Brazil). Clinical information was obtained, and venous blood was taken for ELISA testing (IgA, and IgG antibodies). Sample size consisted of 1,592 military workers (33.6% of study population). They were mostly man (81.2%) and young (median 34 years-old). Most had been asymptomatic (75.3%) during pandemic, and 27.5% reported close contact with COVID-19 cases (after a median time of 21 days). Antibodies were detected in 3.3% of the participants, mostly IgA (2.7%), and IgG (1.7%). After 3 weeks, 66.7% of IgA and IgG results turned negative, in addition to 78.3% and 100% of borderline IgA and IgG results, respectively. CONCLUSION: The seroprevalence of COVID-19 amongst military police was at least 3.4 higher than the findings of other studies performed in the general population, in the same cities and dates. Most detectable antibodies were of IgA class, which implies recent exposure. Asymptomatic people were more prone to have negative antibody titters in the second run.

[Adjuvant chemotherapy after radical liver resection in the treatment of metastases from colorectal carcinoma]. / Ruolo della chemioterapia adiuvante dopo resezione epatica radicale nel trattamento delle metastasi da carcinoma del colon-retto.

Liver metastases are the leading cause of death in patients with colorectal carcinoma: approximately 25% present with metastases at diagnosis of the primary tumor and 30-50% will eventually develop metastases. Surgical therapy for metastases is the only curative treatment that will ensure five-year survival in 30-60% of patients; however, in 30-50% of these patients liver disease will recur. To improve these rates, various different studies have investigated the efficacy of postsurgical adjuvant therapy. The majority of randomized studies evaluated the efficacy of intra-arterial infusion associated or not with postsurgical systemic adjuvant treatment: this approach demonstrated benefit in terms of control of recurrent of liver disease but not in terms of overall survival. A reduction in the recurrence of liver disease was found in the two randomized studies published to date on the efficacy of systemic adjuvant therapy, and an improvement in survival in one trial. Given these data and the results obtained with the use of last generation chemotherapeutic agents (oxaliplatin and irinotecan) in the treatment of unresectable liver metastases from colorectal carcinoma, it can be conjectured that ongoing randomized clinical trials may confirm a significant advantage of adjuvant chemotherapy in the control of recurrence of liver disease and overall survival.

Isolated limb perfusion for the management limb threatening soft tissue sarcomas: The role of histological type on clinical outcomes.

BACKGROUND: Hyperthermic isolated limb perfusion (HILP) is an effective neoadjuvant treatment to avoid amputation in patients with locally advanced extremity soft tissue sarcomas (STS). We aimed to investigate whether STS histological type plays a role in predicting clinical outcomes. METHODS: This study reports a retrospective analysis of 125 patients with limb threatening STS (liposarcoma, n = 41; malignant peripheral nerve sheath tumor, n = 20; leiomyosarcoma, n = 20; miscellany, n = 44), who underwent HILP from 1990 through 2015 at our institution. The following endpoints were evaluated: tumor response (assessed by radiological imaging and histology), limb sparing rate, local progression-free survival (LPFS) and overall survival (OS). RESULTS: On average, overall (complete + partial) tumor response was significantly greater in patients affected with liposarcoma as compared to those with other histotypes (radiological response rate: 38/41, 92.7% vs 66/84, 78.6%, P-value: 0.048; mean histological necrosis: 83.6% vs 52.9%, P < 0.0001). Limb sparing rate was also higher among patients with liposarcoma as compared to other histotypes (39/41, 95.1% vs 62/84, 73.8%, P-value: 0.005). As regards survival, LPFS was similar across tumor types, whereas OS resulted significantly worse in patients with limb leiomyosarcoma (log-rank P-value: 0.009). CONCLUSIONS: HILP is a very effective treatment modality for limb threatening STS. In our series, liposarcoma appears to be the histological type most sensitive to HILP in terms of tumor response and thus limb sparing, which might help clinicians in the patient selection process.

120 peritoneal carcinomatoses from colorectal cancer treated with peritonectomy and intra-abdominal chemohyperthermia: a S.I.T.I.L.O. multicentric study.

A multicentric study has been carried out on 120 patients affected by peritoneal carcinomatosis from colorectal cancer. Patients have been treated by cytoreductive surgery and intra-operative hyperthermic chemoperfusion (HIPEC) with cisplatin (CDDP) and mitomycin-c (MMC). A small group of patients were treated with oxaliplatin (LOHP) following the Elias et al. scheme [intravenous 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) followed by intraperitoneal perfusion with LOHP (460 mg/m2) in 2 l/m2, during 30 min at 43 degrees C]. CC-0 cytoreduction was achieved in 85.2% of the patients. Major morbidity and mortality was 22.5% and 3.3%, respectively. No G4 toxicity was registered. The three-year survival was 25.8%. The difference in survival evaluating complete cytoreduction (CC-0) vs. incomplete (CC1-2; residual tumor nodules greater than 2.5 mm) was statistically significant (p < 0.0001). Evaluating only the patients that could be cytoreduced to CC-0, the 3-year survival was raised to 33.5%. In our experience the peritoneal cancer index (PCI) has been demonstrated to be a weak prognostic factor reaching a statistical significance only after the exclusion of patients with resected hepatic metastases. The patients treated with oxaliplatin were alive and free-of-disease after a 16-month median follow-up.

Sentinel node biopsy and ultrasound scanning in cutaneous melanoma: clinical and technical considerations.

1.5 mm and in all cases with two metastatic SNs, further positive additional nodes were found. The mean counts per 10 s (CP10S) ratio for SN and non-SN values was 5.62 (1.29-23.51) and 3.09 (1.03-10.99) in the intra-operative and extra-operative phases, respectively. US scanning and preoperative lymphoscintigraphy associated with PBD allows preoperative patient selection and accurate SN(s) identification. Breslow thickness and the number of metastatic SN(s), but not their type, are correlated with disease spread; CP10S contributed to the differentiation amongst the nodes and the determining of procedure's completion.

Multimodal treatment of peritoneal carcinomatosis and sarcomatosis.

Peritoneal carcinomatosis and sarcomatosis (PCS) are short-term fatal conditions amenable only to palliative treatment. They are generally considered as a systemic disease at clinical presentation, and are resistant to standard treatments. However, there may be in the natural history a phase of loco-regional tumour spread during which the tumour may still be curable. Surgical treatment alone, or in combination with systemic chemotherapy, has yielded poor results in terms of survival and quality of life. One approach is cytoreductive surgery (CS) combined with the intraperitoneal administration of antiblastic agents. This may diminish any residual tumour following macroscopic excision and may overcome the pharmacokinetic limits of systemic chemotherapy. A further improvement in this multimodal approach may be achieved by the use of hyperthermic intraperitoneal intraoperative chemotherapy (HIIC). Results so far have been encouraging. However, series reported in the literature are relatively small and heterogeneous, and clinical and technical factors which include the selection of patients, optimal drugs dosage and temperature, evaluation of outcome and costs are still under discussion.

Stop-flow technique for loco-regional delivery of antiblastic agents: literature review and personal experience.

AIMS: The therapeutic approach for primary or recurrent advanced solid tumours, particularly when unresectable, is still one of the main medical challenges in the management of cancer patients. The stop-flow (SF) technique has been recently proposed as a semi-invasive drug delivery system based on the blood supply blockage of the tumour-bearing area. Here, we discuss the principles underlying the SF technique as well as the worldwide experience published so far. We also report on the results of our pilot study on pelvic and limb SF perfusion. METHODS: We reviewed the worldwide experience on SF as reported by the literature published on PubMed from 1990 through 2001. In our series, we treated 20 patients affected with locally advanced melanoma, soft tissue sarcoma or colorectal cancer. RESULTS: This therapeutic modality - at least for some tumours - can achieve encouraging results in terms of clinical response even after conventional therapies have failed. Moreover, as a safe and relatively simple procedure, SF can be applied to patients for whom traditional treatments (i.e. surgery, systemic chemotherapy) are contraindicated because of poor general conditions. CONCLUSIONS: At present, the SF technique should be considered an investigational approach to locally advanced cancers. The encouraging results obtained with this procedure should be validated by large phase III trials.

Phase I-II study on isolation antiblastic fotemustine perfusion after dacarbazine chemosensitization for advanced melanoma of the extremities.

Isolation limb perfusion (ILP) is the treatment of choice for locally advanced limb melanoma. With melphalan, the referral drug, complete response (CR) is achieved in about 50% of patients, but significant local toxicity occurs in up to 30%. The aim of the present phase I-II study was to challenge fotemustine (F) in ILP after systemic chemosensitization with dacarbazine (DTIC), given its lower toxicity and greater efficacy, as reported in a previous pilot study. Eleven patients with locally advanced limb melanoma were subdivided into triplets, and given F ILP at escalating doses (starting from 25 mg/l) after intravenous administration of 500 mg/m2 DTIC. Acute and chronic locoregional and systemic toxicity, tumour response and clinical outcome were evaluated. Two patients in the first triplet had G3-G4 local toxicity, so that the scheduled F dosage was halved. At drug levels of 12.5, 15.6 and 18.2 mg/l, local toxicity decreased, but only one of eight patients showed CR. The trial was then interrupted due to the low tolerability and poor efficacy of this perfusion regimen. At present, F ILP after DTIC chemosensitization should not be recommended for the treatment of locally advanced limb melanoma.

Optimized procedure of real-time systemic leakage monitoring during isolated limb perfusion using a hand held gamma probe and 99mTc-HSA.

Isolated limb perfusion (ILP) therapy using a combination of tumour necrosis factor alpha (TNF) and cytostatic agents in hyperthermic conditions has proven to be effective in treating cancers limited to limbs or to a single organ such as the liver. A critical step for ILP is the accurate and real-time monitoring of that TNF toxic effects become relevant when overcoming the 10% limit of the 'effective' therapeutic dose administered during ILP. The most diffuse procedure for systemic leakage monitoring is based on the utilization of human soluble serum albumin (HSA) labelled with 131I and an external scintillation detector. In order to overcome some drawbacks connected with the properties of 131I, we developed a new procedure based on the utilization of HSA labelled with 99mTc in combination with a hand held gamma probe used as a detector. Our procedure consists of the following steps: (1) a 99mTc-HSA dose standardized as 0.5 MBq x kg(-1) body weight is injected into the ILP circuit before TNF administration; (2) a hand held gamma probe is placed over the pre-cordial area in a zone pre-marked on the patient's skin during a simulation test; (3) 48-72 h before ILP, a simulation test is obtained using a 99mTc-HSA dose corresponding to 10% of the dose calculated for ILP (i.e., 0.05 MBq x kg(-1) body weight); (4) during the simulation test the maximum count-rate zone detected on the pre-cordial area is marked on patient's skin; (5) a 60 min time-activity curve corresponding to the circulating 99mTc-HSA radioactivity effective decay is calculated and fitted; and (6) this time-activity curve is used to compensate for the leakage systemic counting observed during ILP. In order to compare the external, probe counting with the circulating radioactivity, in the first 10 patients from a total series of 43 treated patients, the results of external, probe monitoring were compared with the results of patient blood and perfusion circuit samples taken simultaneously every 5 min and measured by a laboratory gamma counter placed in the operating theatre. A good correlation was found between the two methods (R2 = 0.965, P < 0.01). It is concluded that the proposed procedure, based on the combination of 99mTc-HSA as the radiotracer and a hand held gamma probe as the detector, appears to be technically simple and accurate enough in the real-time monitoring of perfusion leakage in ILP cancer therapy. Moreover, using 99mTc-HSA as the radiotracer, the risk of radioactive contamination is significantly lower in comparison with 131I-HSA.

Treatment options for liver metastases from colorectal cancer.

The liver is the most common site of distant metastasis from colorectal cancer. About one-fourth of patients with liver metastases from colorectal cancer have no other sites of metastasis. Surgical resection of colorectal cancer liver metastases can result in a 24%-38% five-year survival. However, only a minority of patients are candidates for resection and no adjuvant treatment has been demonstrated to be effective in increasing the survival rate following radical surgery. For unresectable disease, several treatments have been tested in the clinical setting, although none of them can be currently considered a standard approach. Systemic chemotherapy is not generally considered a treatment for cure, although newer regimens appear to improve median survival. Locoregional therapies such hepatic intra-arterial chemotherapy and isolated hepatic perfusion may be offered to patients with unresectable liver metastases in the absence of extra-hepatic disease. However, the efficacy of these treatments is still being determined. Both systemic and locoregional chemotherapy might be useful in the neoadjuvant setting to increase the resectability of liver metastases initially not amenable to surgical resection.

Sitilo experience on peritoneal carcinomatosis from colorectal cancer: clinical prognostic features.

UNLABELLED: A multicentric prospective study has been carried on 69 patients affected by peritoneal carcinomatosis from colorectal cancer. Patients have been treated by cytoreductive surgery and intraoperative hyperthermic chemoperfusion. CC 0-1 has been achieved in 82%. Major morbidity and mortality was 21.7% and 2.9% respectively. Three-yrs overall survival was 26.7% for all series. Difference in survival evaluating CC 0-1 vs. CC 2 pts and PCI < or = 10 vs. >10 was statistically significant. Evaluating only patients CC 0-1 and PCI < or = 10 4-yrs overall survival rised up to 44.7%. A smaller subgroup of patients with a disease-free interval to peritoneal carcinomatosis > or = 2-yrs showed a 5-yrs disease-free survival of 50%. CONCLUSIONS: PCI < or = 10, complete or optimal cytoreduction feasibility have to be considered for the patients selection to the integrate treatment. Disease-free interval seems to be a powerful prognostic indicator and deserve to be better outlined in further studies.

TNF-based limb perfusion for cutaneous melanoma in transit metastases: suggestions for modification of the perfusional schedule.

Isolated limb perfusion (ILP) is currently considered the standard treatment for melanoma patients with extensive in-transit disease, and L-PAM, combined or not with TNF, represents the most active drug. We here report on our clinical experience with TNF-based limb perfusion. Thirty-seven stage III patients underwent TNF-based limb perfusion, 22 with bulky disease, 15 with recurrences after perfusion with L-PAM. Ten patients were enrolled in a phase I-II study and treated with escalating doses of TNF (0.5-3 mg). The impact of disease burden, temperature, perfusion duration was assessed on tumor response. No postoperative death was observed. No significant systemic toxicity was recorded. Locoregional toxicity was G5 in one patient, G3 in 2, G2 in 9 and G1 in 25. Twenty-four (66%) patients had complete response, 11 (31%) partial and 1 (3%) no change. After a median follow-up of 20 months 14 (38%) patients are NED, 10 (27%) are AWD and 13 (35%) DOD. No significant statistical difference for tumor response were seen for disease burden, ILP temperatures and duration. Our results showed that it is possible to modify the perfusion schedule, without compromising the response rate but with lower cost and toxicity.

Hyperthermic isolated liver perfusion for unresectable liver cancers: pilot study.

Isolated hepatic perfusion (IHP) is a recently reconsidered locoregional approach for unresectable primary or metastatic cancer and encouraging results have been achieved from its clinical application. Ten patients underwent hyperthermic IHP with melphalan. There was no intraoperative mortality. In the postoperative period two patients died due to multi-organ failure. Four patients had significant but transient hepatic toxicity. In 8 assessable patients, the overall response rate was 63%. We observed objective tumor regression in a significant percentage of patients refractory to standard treatments. Locoregional toxicity was significant, which underscores the need for a more accurate preoperative evaluation of hepatic function.

Hyperthermic isolated perfusion with low-dose TNFalpha and doxorubicin in patients with locally advanced soft tissue limb sarcomas.

We report here the results of 27 patients who underwent hyperthermic isolated limb perfusion with low-dose TNFalpha (1 mg) and doxorubicin (8.5 mg/l of limb volume) for locally advanced soft tissue sarcomas. A tumor response was observed in 85% of cases. After a median follow-up of 30 months, limb salvage and local disease control were achieved in 82 and 85% of patients, respectively. Locoregional toxicity was low or mild in 14 patients, while 2 patients had severe limb toxicity. Systemic side effects were negligible. The perfusate/plasma area under the curve (AUC) ratio for TNFalpha was 56. HILP with low-dose TNFalpha and DXR proved to be an active neoadjuvant drug regimen against limb-threatening STS.

A simplified procedure for continuous intraoperative external monitoring of systemic leakage during isolated limb perfusion.

AIMS: Isolated limb perfusion (ILP) with high doses of an alkylating agent alone or in combination with tumor necrosis factor (TNF) in hyperthermic conditions (HAP) has been proposed for the treatment of locoregional tumors. A critical step in ILP/HAP is accurate monitoring of systemic leakage to prevent the toxic effects of chemotherapy, and in particular of TNF. Ten percent systemic leakage from the perfusion circuit is considered the maximum acceptable leakage. In this study we report our experience of a new leakage monitoring system. MATERIALS AND METHODS: Ths new simplified procedure is based on the use of 99mTc-labeled soluble human serum albumin (HSA) and a hand-held gamma probe as detector. The procedure consists of the following steps: 1) A standardized 99mTc-HSA dose of 0.5 MBq/kg body weight is injected into the perfusion circuit before chemotherapy/TNF perfusion and a hand-held gamma probe (IGP) is placed over the precordial area in a zone that was marked on the skin during a simulation test; 2) 48-72 hours before ILP/HAP a complete simulation test is performed with a 99mTc-HSA dose corresponding to 10% of the total dose calculated for the patient's body weight; 3) during the simulation test the maximum count-rate zone on the precordial area is detected by IGP and marked on the patient's skin; 4) a 60-min curve of effective 99mTc-HSA radioactivity decay (physical and biological) is calculated and fitted; 5) to compare external counting with the effective circulating radioactivity, patient blood samples and circuit blood samples are taken every five minutes during ILP/HAP and measured by a laboratory gamma counter and very convenient thanks to the favorable characteristics of IGP. The placed in the operating room. RESULTS: External counting with a hand-held gamma probe was easy to perform time/activity curves obtained during simulation tests showed a regular and constant effective decay with a mean decay rate of 30% at 60 minutes compared to baseline values. The external measurements obtained by IGP proved to be well correlated with blood samples measured in vitro by a laboratory gamma counter. The results of this procedure, in particular the data of the simulation test for each patient, allowed us to correct the limit of 10% maximum leakage during ILP/HAP in accordance with the time/activity curve. CONCLUSIONS: Although 99mTc-HSA has some unfavorable characteristics, it offers many advantages over 131I-HSA. The procedure proposed by us, which was based on the use of an IGP and 99mTc-HAS at a standardized dose of 0.5 MBq/kg body weight and on an individual simulation test for each patient performed 48 hours before ILP/HAP, proved to be simple and accurate in monitoring systemic leakage during ILP/HAP anti-cancer therapy.

[Indications for integrated surgical treatment of peritoneal carcinomatosis of colorectal origin: experience of the Italian Society of Locoregional Integrated Therapy in Oncology]. / Indicazioni al trattamento chirurgico integrato delle carcinosi peritoneali di origine colorettale: esperienza della società Italiana di terapie integrate locoregionali in oncologia.

A multicentric prospective study has been carried on 69 patients affected by peritoneal carcinomatosis from colorectal cancer. Patients have been treated by cytoreductive surgery and intraoperative hyperthermic chemoperfusion. CC 0-1 has been achieved in 82%. Major morbidity and mortality was respectively 21.7% and 2.9%. Three years overall survival was 26.7% for all series. Difference in survival evaluating CC 0-1 vs CC 2 patients and PCI < or = 10 vs > 10 was statistically significant. Evaluating only patients CC 0-1 and PCI < or = 10 overall survival rised up to 44.7% at 4 years. A smaller subgroup of patients with a disease-free interval to peritoneal carcinomatosis > or = 2-year showed a 50% disease-free survival at 5 years. In conclusion PCI < or = 10, complete or optimal cytoreduction feasibility and disease-free interval have to be considered for the patients selection to the integrate treatment.

Sentinel node biopsy in cutaneous melanoma patients: technical and clinical aspects.

The role of the patent blue dye (PBD) technique and intraoperative probe-guided lymphoscintigraphy (LS) in detecting the sentinel node (SN) was investigated in a group of 130 consecutive stage I cutaneous melanoma patients. The preoperative workup included high-resolution US scanning and LS performed 15-18 hours before surgery. On the basis of preoperative LS, in the group of examined patients a total of 143 lymphatic drainage basins were identified and surgically explored: 41.6% in the axilla, 52.8% in the groin, and 5.6% in the head/neck. A total of 228 SNs were intraoperatively detected and removed; 110 lymphatic basins contained histologically negative SNs, while 33 basins had metastatic SNs. The sensitivity for SN detection using PBD alone was 93%, while it was 100% when PBD was combined with intraoperative LS. Preoperative and intraoperative LS appears to be a highly sensitive technique for SN detection in cutaneous melanoma patients. Furthermore, in view of the limited skin incision when radioguided surgery is performed, SN biopsy could be feasible under local anesthesia.

[Complementary treatment to surgery of gastric carcinoma: role of adjuvant and neoadjuvant chemotherapy]. / Terapie complementari al trattamento chirurgico del carcinoma gastrico: ruolo della chemioterapia adiuvante e neoadiuvante.

Although there has been a decline in the incidence of gastric cancer worldwide, its mortality rate is still high. In the West, attempts with adjuvant chemotherapy to improve survival have been disappointing. The promising results reported with the FAM (5-FU, Adriamycin, Mitomycin C) regimen in patients with advanced disease, have not been confirmed in an adjuvant setting. Randomized trials on adjuvant chemotherapy in Japan have shown a positive outcome in treated patients only when subgroups with advanced disease are considered. As results with adjuvant chemo-immunotherapy were better than those with chemotherapy alone, immunostimulators have been widely utilized in clinical trials conducted in Japan in recent years. However, chemo-immunotherapy may be more effective in patients with minimal residual disease, due to the combined action of a lower stage at diagnosis and to a diffuse application of standard wide lymphadenectomy. Inadequate lymphadenectomy, like that performed in many western studies, may compromised radicality in patients with "curable" disease and the concept of "minimal residual disease" must therefore be considered in future trials on adjuvant chemotherapy. Future trends for new therapeutic combinations (FAMTX, EAP, 5-FU/Cisplatin, PELF, etc) tested in phase II and III clinical trials are also discussed. Whatever the type of approach used, the high incidence of intra-abdominal recurrences indicates that an improvement in the prognosis of patients with advanced diseases will only come with the development of additional treatment modalities such as neoadjuvant or intraperitoneal chemotherapy.