Deep diving in the PACIFIC: Practical issues in stage III non-small cell lung cancer to avoid shipwreck.

After publication of the PACIFIC trial results, immune checkpoint inhibitor-based immunotherapy was included in the treatment algorithm of locally advanced non-small cell lung cancer (NSCLC). The PACIFIC trial demonstrated that 12 mo of durvalumab consolidation therapy after radical-intent platinum doublet chemotherapy with concomitant radiotherapy improved both progression-free survival and overall survival in patients with unresectable stage III NSCLC. This is the first treatment in decades to successfully improve survival in this clinical setting, with manageable toxicity and without deterioration in quality of life. The integration of durvalumab in the management of locally advanced NSCLC accentuates the need for multidisciplinary, coordinated decision-making among lung cancer specialists, bringing new challenges and controversies as well as important changes in clinical work routines. The aim of the present article is to review-from a practical, multidisciplinary perspective-the findings and implications of the PACIFIC trial. We evaluate the immunobiological basis of durvalumab as well as practical aspects related to programmed cell death ligand 1 determination. In addition, we comprehensively assess the efficacy and toxicity data from the PACIFIC trial and discuss the controversies and practical aspects of incorporating durvalumab into routine clinical practice. Finally, we discuss unresolved questions and future challenges. In short, the present document aims to provide clinicians with a practical guide for the application of the PACIFIC regimen in routine clinical practice.

Multicenter phase II clinical trial of preoperative capecitabine with concurrent radiotherapy in patients with locally advanced rectal cancer.

INTRODUCTION: To assess pathologic complete response, sphincter preservation rates and toxicity profile of preoperative chemoradiation with capecitabine in resectable locally advanced rectal cancer. MATERIALS AND METHODS: Fifty-eight patients from six Spanish centers were included (March 2004 to June 2005) with histological/cytological diagnosis of locally advanced rectal cancer, age between 18 and 80 years, ECOG 0-2, adequate bone marrow, renal and hepatic functions. Prior chemotherapy/radiotherapy was not allowed. Preoperative treatment was capecitabine 825 mg/m(2) bid concomitant to radiotherapy (45 + 5.4 Gy boost over 5.5 weeks). Surgery was performed 4-8 weeks after completion of chemoradiotherapy. RESULTS: Fifty-eight patients were enrolled in this study: 60.3 % males, median age of 64.5 (30.9-78.7) years, 28.6 % with ECOG 0 and 71.4 % with ECOG 1. Median distance of tumor from the anal verge was 7 (1-12) cm. Fifty-two (89.6. %) patients completed preoperative chemoradiotherapy. Primary tumor and node downstaging occurred in 61.1 and 69.6 % of patients, respectively. Surgery was performed in 55 patients (94.8 %): 80 % had negative lymph nodes and 72.7 % underwent sphincter-preserving procedures. A pathologic complete response was observed in 10.5 % (95 % CI 2.5-18.5) of the patients. Main grade I-II toxicities were leucopenia (43.1 %), neutropenia (24.1 %), anemia (36.2 %), diarrhea (32.8 %) and skin disorders (5.1 %), from which diarrhea (6.9 %), leucopenia (1.7 %) and skin disorders (1.7 %) reached grade III. There were no grade IV toxicities. CONCLUSIONS: Preoperative capecitabine-based chemoradiation is a well-tolerated and effective neoadjuvant treatment for locally advanced rectal cancer that achieves encouraging rates of tumor downstaging.

Damage assessment in gastric cancer treatment with adjuvant radiochemotherapy: calculation of the NTCP's from the differential HDV of the organs at risk.

OBJECTIVE: To calculate the Normal Tissue Complication Probabilities (NTCP) for the liver, right kidney, left kidney and spinal cord, as well as the global Uncomplicated Tumour Control Probability (UTCP) in gastric cancer patients who underwent a treatment with radiotherapy after radical surgery in our environment. MATERIAL AND METHOD: In April 2000, a postoperative chemotherapy (QT-RT) protocol started in the province of Malaga for Gastric Adenocarcinomas with postsurgical stage II or higher (pT3-4 and/or pN+). This clinical protocol served as a base for our NTCP and UTCP retrospective theorical study. A virtual simulation and a 3D planning were made in all cases. The differential HDV, selected for each patient were obtained for the 4 organs at risk (OR). Hystograms reduction was made by the Kutcher and Burman's Effective Volume method. NTCP calculations by Lyman's models. The following variables were calculated: maximal dose for each organ (Dmax), Effective Volume (Veff), TD50 (Veff/Vref); NTCP for each organ of the patient; global UTCP for each patient. Differences between the 2 treatment techniques were analysed (2-field versus 4-field technique). For the NTCP calculations the computer application Albireo 1.0(R) was used. RESULTS: 29 patients to assess with an average age of 54 +/- 10 years (range: 38-71); 65.5% men/34.5% women. The technique used was the field technique AP-PA in the 51.7% (15) and with 4 fields in 48.3% (14) of the cases. The global damage is estimated in 16% with a range between 0 and 37%. This goes up to 25% with the 2-field technique, with a wide range between 2 and 48% and it remains reduced to 4%, within a range between 0 and 12% when 4 fields are used. There were significant differences concerning the estimated damage probability (NTCP) on liver, spinal cord and left kidney, depending on the use of two or four fields. CONCLUSION: NTCP and the global UTCP values of the organs at risk allow to compare a technique net benefit from another in each particular case, although in our theoretical study the comparison was done among the patients. It is important to stress that the calculations of the TCP and NTCP have a limited quantitative signification but they are useful and beneficial in order to decide between treatment plans when they are supported by the clinical knowledge.

Damage assessment in gastric cancer treatment with adjuvant radiochemotherapy: calculation of the NTCP´s from the differential HDV of the organs at risk

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Objective. To calculate the Normal Tissue ComplicationProbabilities (NTCP) for the liver, right kidney,left kidney and spinal cord, as well as theglobal Uncomplicated Tumour Control Probability(UTCP) in gastric cancer patients who underwenta treatment with radiotherapy after radical surgeryin our environment.Material and method. In April 2000, a postoperativechemotherapy (QT-RT) protocol started in theprovince of Malaga for Gastric Adenocarcinomaswith postsurgical stage II or higher (pT3-4 and/orpN+). This clinical protocol served as a base forour NTCP and UTCP retrospective theorical study.A virtual simulation and a 3D planning were madein all cases. The differential HDV, selected for eachpatient were obtained for the 4 organs at risk (OR).Hystograms reduction was made by the Kutcherand Burman's Effective Volume method (1989; 1991).NTCP calculations by Lyman's models (1985). Thefollowing variables were calculated: maximal dosefor each organ (Dmax), Effective Volume (Veff),TD50 (Veff/Vref); NTCP for each organ of the patient;global UTCP for each patient. Differencesbetween the 2 treatment techniques were analysed(2-field versus 4-field technique). For the NTCPcalculations the computer application Albireo 1.0®was used.Results. 29 patients to assess with an average ageof 54 ± 10 years (range: 38-71); 65.5% men/34.5%women. The technique used was the field techniqueAP-PA in the 51.7% (15) and with 4 fields in48.3% (14) of the cases. The global damage is estimatedin 16% with a range between 0 and 37%.This goes up to 25% with the 2-field technique,with a wide range between 2 and 48% and it remainsreduced to 4%, within a range between 0and 12% when 4 fields are used.There were significant differences concerning theestimated damage probability (NTCP) on liver,spinal cord and left kidney, depending on the useof two or four fields.Conclusion. NTCP and the global UTCP values ofthe organs at risk allow to compare a techniquenet benefit from another in each particular case,although in our theorical study the comparisonwas done among the patients. It is important tostress that the calculations of the TCP and NTCPhave a limited quantitative signification but theyare useful and beneficial in order to decide betweentreatment plans when they are supported bythe clinical knowledge