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\title{Urinary and Digestive Toxicities of 3D Conformal Radiotherapy of Localized Prostate Cancer at the Pointe a Pitre University Hospital in Guadeloupe}
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             \author[1]{Ibrahima  Thiam}

             \author[2]{nta  Ka}

             \author[3]{Boucar  Ndong}

             \author[4]{El Hadj Amadou  Sall}

             \author[5]{Ousseynou  Sarr}

             \author[6]{Mahomed  Yessoufou}

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\date{\small \em Received: 10 February 2021 Accepted: 5 March 2021 Published: 15 March 2021}

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\begin{abstract}
        


Introduction: At present, despite the advent of innovative methods such as IMRT, which improves therapeutic performance while reducing toxicity, RC3D is still widely used, especially in developing countries. The objective of this work was to evaluate the urinary and digestive toxicities of RC3D on prostate cancers located at the Pointe à Pitre University Hospital in Guadeloupe in order to position this technique in the therapeutic arsenal. Materials and methods: We conducted a retrospective study of 29 patients with localized prostate cancer treated with RC3D. The endpoint was urinary and digestive toxicities. Materials and methods:We conducted a retrospective study of 29 patients with localized prostate cancer treated with RC3D. The endpoint was urinary and digestive toxicities.

\end{abstract}


\keywords{toxicities, radiotherapy, cancer, prostate.}

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\let\tabcellsep& 	 	 		 
\section[{Introduction}]{Introduction}\par
rostate cancer is the second most diagnosed cancer in men after lung cancer with 13.7\% of cases \hyperref[b0]{[1]}. Its incidence is high in Guadeloupe \hyperref[b1]{[2]}. The treatment of prostate cancer is multidisciplinary, with radiotherapy and surgery as the main curative methods.\par
Radiotherapy is said to be conformal when the dose of ionising radiation used is delivered homogeneously to a precisely defined tumor volume while sparing healthy tissue and surrounding organs as much as possible. This is achieved through initial threedimensional imaging for location and repositioning. The precise calculation of the dose to be delivered is achieved through computer-controlled multi-blade collimators.\par
Thanks to the progress made by conformal radiotherapy, the results obtained are becoming similar in terms of disease control to those of surgery, as shown by several comparative series. Radiotherapy has therefore become an essential technique in the treatment of prostate cancer despite its complications, notably urinary and digestive \hyperref[b2]{[3]}. In this paper, we evaluate these complications that arise during the management of localised prostate cancer treated with 3D conformal radiotherapy. 
\section[{II.}]{II.} 
\section[{Patients and Method a) Patients}]{Patients and Method a) Patients}\par
This was a descriptive, retrospective study that took place at the Radiotherapy Department of the Pointe à Pitre University Hospital in Guadeloupe, carried out over a period of one year (January 2015 to December 2015).\par
A total of 29 patients consulting for localized prostate cancer with a negative distant extension assessment were treated with 3D radiotherapy plus or minus hormone therapy. These patients had not received any previous specific treatment and their characteristics are summarised in Table  {\ref I}. 
\section[{b) Method}]{b) Method}\par
Data were collected using archived medical records, from the Varian Aria software and Easily from the CHU Guadeloupe. A data collection form was drawn up for this purpose.\par
The data were entered and analysed on Epi info 7 on Microsoft Excel 2007. Histograms and other figures were produced with Microsoft Excel 2007. 
\section[{III.}]{III.} 
\section[{Results}]{Results}\par
The median age of the patients was 75 years. The most common comorbidity was hypertension, which was found in 23 patients (79.31\%). The diagnosis was made on the basis of urinary symptoms in 10 patients (34\%). They were generally in good general condition. The median PSA level was 12 ng/ml with extremes of 3.05 and 79 ng/ml. Histological examination revealed adenocarcinoma in all patients. The Gleason score was heterogeneous with a score of 6 (3+3) in 6 patients (20, 69\%), a score of 7 (3+4) in 12 patients (41, 38\%) and another score of 7 (4+3) in 11 patients (37, 93\%).\par
A loco-regional extension assessment by MRI was performed in 26 patients (89, 66\%) and contraindicated in 3 patients. On imaging, we found T3a in 5 patients (19, 23\%), T3b in 4 patients (15, 38\%) and lymph node involvement in 1 patient (3, 8\%). Thoracoabdomino-pelvic CT was performed in 9 patients (31.03\%) and scintigraphy in 25 patients (86.21\%).\par
The D'AMICO classification was established for all patients. It is a major criterion in the therapeutic decision.\par
Thus, 3 patients (10.34\%) were classified as low risk, 12 patients (41.38\%) as intermediate risk and 14 patients (48.28\%) as high risk Among the patients classified as intermediate risk, 7 were of favourable intermediate risk and 5 unfavourable intermediate.\par
All our patients had received 3D conformal radiotherapy for curative purposes. It was associated or not with hormone therapy. The time to treatment was defined as the time from the date of diagnosis to the start of radiotherapy.\par
The median time was 5.7 months (2.3-23) and the mean time was 6.4 months.\par
Pelvic irradiation was performed in 15 patients (51.72\%). The median total dose delivered was 74 Gy, with a mean dose of 73.79 Gy and extremes of 70 Gy for the minimum and 76 Gy for the maximum.\par
In all our patients, conventional fractionation was used, i.e. 2 Gy per fraction, 5 days a week.\par
Hormone therapy was combined with radiotherapy in 17 patients (58.62\%). All patients in the D'AMICO high-risk group had received long hormonal therapy and 3 patients in the intermediate-risk group had received short hormonal therapy.\par
The median follow-up after radiotherapy was 56 months (28-66 months). The median follow-up was 63 months (27.5-74.3 months).\par
Toxicities were assessed according to the RTOG criteria. Acute toxicity was defined as all toxicities occurring during treatment and up to 3 months after the end of treatment and all those occurring beyond 3 months were late. Thus, acute bladder toxicity was found in 7 patients (24.14\%) with grade 1 acute toxicity and 1 patient (3.45\%) with grade 2 acute toxicity. For acute rectal toxicity, all the patients had tolerated the treatment well in terms of digestion, with grade 1 symptoms in 7 patients (24.14\%), then for late bladder toxicity grade 1, we found 5 patients (17.24\%), 3 patients (10.34\%) for grade 2 and 1 patient for grade 3, i.e. 3.45\%. And finally, for late rectal toxicity grade 2, we found 3 patients (10.34\%) and 1 patient grade 3. 
\section[{IV.}]{IV.} 
\section[{Discussion}]{Discussion}\par
The constant progress of irradiation techniques has mainly allowed an increase in the dose to the target volumes and a reduction of the dose to the organs at risk. Dearnaley et al. in a randomised study reported a reduction in GI toxicity in favour of 3DR compared to conventional radiotherapy with 56\% grade 1 rectitis versus 37\% and 12\% versus 3\% for grade 2 \hyperref[b3]{[4]}. Koper et al, with the same comparison, found less intestinal toxicity, especially in the anus, in patients treated with RC3D \hyperref[b4]{[5]}.\par
Pelvic irradiation is a much debated topic with conflicting results from several retrospective studies, its toxicity remains quite acceptable \hyperref[b2]{[3]}.\par
Several randomised studies have shown that the risk of rectal toxicity was greater when a high dose of radiation (78-80 Gy) was delivered to the prostate compared to a standard dose (70 Gy) \hyperref[b6]{[6,}\hyperref[b7]{7]}.\par
Regarding urinary toxicity, most randomised studies comparing a "standard" dose (70 Gy) with a high dose (78-80 Gy) did not find a significant increase in urinary toxicity, except for the French Gétug study 06 \hyperref[b6]{[6]}\hyperref[b7]{[7]}\hyperref[b8]{[8]}\hyperref[b10]{[9]}. The lack of a clear conclusion regarding urinary toxicity may have several explanations. The main urinary manifestations seem to be of urethral rather than bladder origin. The urethra is consistently included in the high-dose volume treated and exceptionally delineated as such \hyperref[b11]{(10)}.\par
The median dose in our series was 74 Gy and 51.72\% of patients had received pelvic irradiation.\par
The radiotherapy was well tolerated by the patients, no acute urinary or digestive toxicity of grade > 2 was noted in our series as in the study by Peeters et al \hyperref[b10]{[9]}. Indeed, acute urinary toxicity grade 1 and 2 were respectively 24.14\% and 3.45\% and digestive toxicity was grade 1 in 10 patients (34.48\%). These results are lower than those reported by Pollack, Beckendorf, Peeters and Elie Nasr which could be explained by the small number of patients \hyperref[b8]{(8,}\hyperref[b10]{9,}\hyperref[b12]{11,}\hyperref[b13]{12)}. Late toxicity was relatively lower than in the literature (Table \hyperref[tab_1]{2}-3).\par
Intensity-modulated conformal radiotherapy significantly reduces late grade 2 GI toxicity without impacting on urinary toxicity with dose escalation \hyperref[b14]{[13]}. IMRT provides better coverage of the target volume with good sparing of organs at risk, particularly for the rectum according to the study by Pascal Fenoglietto et al \hyperref[b15]{[14]}. Wang-Chesebro et al. demonstrated with pelvic IMRT a dose reduction in the bladder, V45 Gy (volume receiving 45 Gy) of 90\%, 54\% for the rectum V45 Gy and 54\% of the small bowel V45 Gy compared to threedimensional conformal radiotherapy \hyperref[b17]{[15]}.\par
V. 
\section[{Conclusion}]{Conclusion}\par
Despite the good results obtained with RC3D, intensity modulated radiotherapy (IMRT and VMAT) with rigorous verification of the treatment position is the indicated technique for the treatment of prostate cancers. It allows dose escalation to target volumes with acceptable toxicity.  \begin{figure}[htbp]
\noindent\textbf{1} \par 
\begin{longtable}{P{0.4533333333333333\textwidth}P{0.39666666666666667\textwidth}}
Characteristics of patients\tabcellsep Headcount (percent)\\
Median age (years)\tabcellsep 75 (54 -83)\\
HTA\tabcellsep 23 (79.31\%)\\
Diabetes\tabcellsep 12 (41.38\%)\\
Heart disease\tabcellsep 3 (10.34\%)\\
CRI\tabcellsep 1 (3.45\%)\\
Systematic screening\tabcellsep 19 (65.52\%)\\
Urinary signs\tabcellsep 10 (34.48\%)\\
Performance status\tabcellsep \\
0\tabcellsep 20 (69\%)\\
1\tabcellsep 8 (28\%)\\
2\tabcellsep 1 (3\%)\\
TR abnormal\tabcellsep 15 (51.72\%)\\
Median PSA (ng/ml)\tabcellsep 12 (3.05 -79)\\
Gleason\tabcellsep \\
-6 (3 + 3)\tabcellsep 6 (20.69\%)\\
-7 (3 + 4)\tabcellsep 12 (41.38\%)\\
-7 (4 + 3)\tabcellsep 11 (37.93\%)\\
Classification of D'AMICO\tabcellsep \\
-High risk\tabcellsep 14 (48.28\%\\
-Low risk\tabcellsep 3 (10.34\%)\\
-Middle risk\tabcellsep 12 (41.38\%)\end{longtable} \par
 
\caption{\label{tab_0}Table 1 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{2} \par 
\begin{longtable}{P{0.13089668615984404\textwidth}P{0.0530214424951267\textwidth}P{0.0712475633528265\textwidth}P{0.30321637426900583\textwidth}P{0.05799220272904483\textwidth}P{0.23362573099415201\textwidth}}
\tabcellsep Number of patients\tabcellsep Dose (Gy)\tabcellsep Acute urinary toxicity\tabcellsep Median follow-up (month)\tabcellsep Late urinary toxicity\\
\tabcellsep \tabcellsep \tabcellsep G1 44\% vs 42\%\tabcellsep \tabcellsep G1 22\% vs 27\%\\
Beckendorf et al (8)\tabcellsep 306\tabcellsep 70 vs 80\tabcellsep G2 31\% vs 30\%\tabcellsep 57\tabcellsep G2 8\% vs 16\%\\
\tabcellsep \tabcellsep \tabcellsep G3 5\% vs 7\%\tabcellsep \tabcellsep G3 2\% vs 1\%\\
\tabcellsep \tabcellsep \tabcellsep G1 43\% vs 42\%\tabcellsep \tabcellsep \\
Pollack et al (11)\tabcellsep 301\tabcellsep 70 vs 80\tabcellsep G2 31\% vs 23\%\tabcellsep 72\tabcellsep ?G2 10\% vs 10\%\\
\tabcellsep \tabcellsep \tabcellsep G3 3\% vs 5\%\tabcellsep \tabcellsep \\
\tabcellsep \tabcellsep \tabcellsep G1 40\% vs 42\%\tabcellsep 36\tabcellsep ?G2 29\% vs 30\%\\
Peeters et al (9)\tabcellsep 669\tabcellsep 68 vs 78\tabcellsep G2 13\% vs 13\%\tabcellsep \tabcellsep ?G2 41\% vs 40\%\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep 84\tabcellsep \\
Elie Nasr(12)\tabcellsep 131\tabcellsep 66-74\tabcellsep G1 31,3\%\tabcellsep \tabcellsep \\
\tabcellsep \tabcellsep \tabcellsep G2 16,8\%\tabcellsep -\tabcellsep -\\
\tabcellsep \tabcellsep \tabcellsep G3 2,3\%\tabcellsep \tabcellsep \\
\tabcellsep \tabcellsep \tabcellsep G1 24,14\%\tabcellsep \tabcellsep G1 17,24\%\\
Notre étude\tabcellsep 29\tabcellsep 70-74\tabcellsep G2 3,45\%\tabcellsep 56\tabcellsep G2 10,34\%\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep G3 3,45\%\end{longtable} \par
 
\caption{\label{tab_1}Table 2 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{3} \par 
\begin{longtable}{P{0.13530612244897958\textwidth}P{0.05551020408163266\textwidth}P{0.07459183673469387\textwidth}P{0.28622448979591836\textwidth}P{0.06071428571428571\textwidth}P{0.23765306122448981\textwidth}}
\tabcellsep Number of patients\tabcellsep Dose (Gy)\tabcellsep Acute digestive toxicity\tabcellsep Median follow-up (month)\tabcellsep Toxicité digestive tardive\\
\tabcellsep \tabcellsep \tabcellsep G1 43\% vs 37\%\tabcellsep \tabcellsep G1 23\% vs 25\%\\
Beckendorf et al\tabcellsep 306\tabcellsep 70 vs 80\tabcellsep G2 27\% vs 28\%\tabcellsep 57\tabcellsep G2 12\% vs 16\%\\
(8)\tabcellsep \tabcellsep \tabcellsep G3 2\% vs 2\%\tabcellsep \tabcellsep G3 2\% vs 6\%\\
\tabcellsep \tabcellsep \tabcellsep G1 43\% vs 39\%\tabcellsep \tabcellsep \\
Pollack et al (11)\tabcellsep 301\tabcellsep 70 vs 80\tabcellsep G2 38\% vs 39\%\tabcellsep 72\tabcellsep ?G2 12\% vs 26\%\\
\tabcellsep \tabcellsep \tabcellsep G3 2\% vs 0\%\tabcellsep \tabcellsep \\
Peeters et al (9)\tabcellsep \tabcellsep \tabcellsep G1 41\% vs 47\%\tabcellsep 36\tabcellsep ?G2 23\% vs 27\%\\
\tabcellsep 669\tabcellsep 68 vs 78\tabcellsep G2 6\% vs 4\%\tabcellsep 84\tabcellsep ?G2 25\% vs 35\%\\
Elie Nasr(12)\tabcellsep 131\tabcellsep 66-74\tabcellsep G1 27,5\%\tabcellsep \tabcellsep \\
\tabcellsep \tabcellsep \tabcellsep G2 9,1\%\tabcellsep -\tabcellsep -\\
Notre étude\tabcellsep 29\tabcellsep 70-74\tabcellsep G1 24,14\%\tabcellsep \tabcellsep G2 10,34\%\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep 56\tabcellsep G3 3,45\%\end{longtable} \par
 
\caption{\label{tab_2}Table 3 :}\end{figure}
 		 		\backmatter  			 			 			  				\begin{bibitemlist}{1}
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\end{document}
